Herbicidal compositions comprising 2- (4-heterocyclic-phenoxymethyl)Phenoxy!-alkanoates

ABSTRACT

Herbicidal compounds, compositions containing them, and a method for controlling weeds by application of the compositions are disclosed. The herbicidal compounds are 2- (4-heterocyclic-phenoxymethyl)phenoxy!alkanoates of the formula ##STR1## in which A is a derivative of an alkanoate bonded to the phenoxy oxygen at the alpha carbon; X is hydrogen, methyl, fluorine, or chlorine; Y is hydrogen; W is oxygen or sulfur; Z is hydrogen, fluorine, chlorine, bromine, lower alkyl, or methoxy; Z&#39; is hydrogen, fluorine, or chlorine; and the group AO-- may be in the 2, 3, or 4-position of the phenyl ring.

This invention pertains to novel herbicidal 2-(4-heterocyclic-substituted-3-halophenoxymethyl)phenoxy!alkanoates,especially propionates and acetates, and their use for weed control inagriculture, horticulture, and other fields in which it is desired tocontrol unwanted plant growth, such as grassy or broadleaf plantspecies. In particular, it pertains to those compounds in which theheterocyclic moiety is selected from among4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl,3,4,5,6-tetrahydrophthalimid-1-yl,1-(1-methylethyl)imidazolidin-2,4-dion-3-yl,1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-on-1-yl,3-chloro-4,5,6,7-tetrahydroindazol-2-yl,4-methyl-1,2,4-triazine-3,5-dion-2-yl, 8-thia-1,6-diazabicyclo4.3.0!nonane-7-on-9-ylimino, and1-methyl-6-trifluoromethyl-2,4-pyrimidinedione-3-yl groups. Thesecompounds are both pre- and postemergence herbicides. The use of thisclass of compounds as herbicides has not previously been described.

U.S. Pat. No. 5,084,085 discloses compounds of the formula: ##STR2##wherein R^(a) is preferably lower haloalkyl, and R^(b) is preferablylower alkyl;

R' and R² are broadly defined;

X and Y are independently halogen, alkyl, alkoxy, alkylthio, haloalkyl,nitro, cyano, sulfonylalkyl, or --SOCF₃ ;

M is CH or N; and

A is a derivative of an alkanoate bonded to the phenoxy oxygen at thealpha carbon.

U.S. Pat. No. 4,816,065 discloses compounds like those of U.S. Pat. No.5,084,085, except that the triazolinone ring has been replaced by a3,4,5,6-tetrahydrophthalimido moiety. Similarly, U.S. Pat. No. 4,885,025discloses compounds in which the triazolinone ring of U.S. Pat. No.5,084,085 has been replaced with a tetrazolinone moiety.

U.S. Pat. No. 3,984,434, Japanese patents 54-25018, 54-26534, and60-39668, and Japanese patent applications 49-000432 and 54-19965, allassigned to Mitsubishi Chemical Industries, Ltd., disclose compounds ofthe general formula: ##STR3## wherein X is hydrogen, halogen, nitro,alkyl, or alkoxy,

Y is hydrogen, halogen, alkyl, and n and m are each 1 to 4.

It has,now been found that 2-(4-heterocyclic-substituted-3-halophenoxymethyl)phenoxy!alkanoates areunexpectedly active as both pre- and postemergence herbicides. Inparticular, as preemergence herbicides many of these compounds exhibittolerance of soybeans and, to a certain extent, of corn. Perhaps ofgreater interest is the postemergence activity, where no crop toleranceis exhibited, making them excellent candidates as total vegetationcontrol agents.

The novel 2-(4-heterocyclic-substituted-3-halophenoxymethyl)phenoxy!alkanoates ofthe present invention are described by the following generic structure:##STR4## wherein A is ##STR5## Q is selected from the followingheterocycles: ##STR6## W is oxygen or sulfur; X is selected fromhydrogen, methyl, fluorine, or chlorine;

Y is hydrogen, or

X and Y taken together may be --O--C(CH₃)₂ CH₂ -- to form a7-substituted-4-benzofuranyl moiety;

R' is hydrogen or methyl;

R" is --OR or amino, arylamino (e.g. phenylamino), alkylamino (e.g.lower alkylamino such as methylamino or dimethylamino), alkenylamino(e.g. lower alkenylamino such as diallylamino), alkoxyamino (e.g. loweralkoxyamino such as methoxyamino), cyano, or alkyl-, haloalkyl-, orarylsulfonylamino of the formula --N(lower alkyl)SO₂ R⁹, or --NHSO₂ R⁹ ;

R is hydrogen, M, alkyl (e.g., lower alkyl such as methyl or ethyl),cycloalkyl, lower alkenyl or lower alkynyl, each optionally substitutedwith one or more chlorine or fluorine, or -- CHR⁷ (CH₂)_(m) O!_(n) R⁸,each of R¹ through R⁶ is lower alkyl or lower haloalkyl;

R⁷ is hydrogen or lower alkyl;

R⁸ is alkyl, preferably lower alkyl;

R⁹ is alkyl (e.g. lower alkyl such as methyl, ethyl or propyl),haloalkyl (e.g. halo lower alkyl such as trifluoromethyl), or aryl suchas phenyl or substituted phenyl, (e.g. lower alkoxy-substituted and/orhalo-substituted phenyl);

m is 0 to 2, preferably 0 to 1, and n is 1 to 6, preferably 1 to 3; and

M is a monovalent, salt-forming group such as sodium, potassium, orammonium;

Z is hydrogen, fluorine, chlorine, bromine, lower alkyl, phenyl, ormethoxy;

Z' is hydrogen, fluorine, or chlorine; or

Z and Z' taken together may be --(CH₂)₄ -- to form a tetrahydronaphthylmoiety; and

the group A--O-- may be in the 2, 3, or 4-position of the phenyl ring.

Preferred compounds are those in which R" is --OR and Z is chlorine orlower alkyl.

Particularly preferred are those compounds in which R is lower alkyl,lower chloroalkyl, or -- CHR⁷ (CH₂)_(m) O!_(n) R⁸ ; R¹ isdifluoromethyl; R² is methyl; R³ is 1-methylethyl; R⁴ is 3-fluoropropyl;R⁵ is methyl; R⁶ is methyl; R⁷ is H or CH₃ ; R' is methyl; Z is in the4-position; Z' is hydrogen or chlorine in the 3-position; m is 0 or 1,and n is 1 to 3; and the group AO-- is in the 2-position of the phenylring.

Many of the compounds of the invention were prepared by the followingreaction: ##STR7##

An appropriately substituted methyl 2-(chloromethylphenoxy)alkanoate andan appropriately substituted 4-heterocyclic-substituted phenol wereheated in N,N-dimethylformamide at 80° C. in the presence of at least amolar equivalent of potassium carbonate. Usually the reaction was runovernight. Preparation of the corresponding acid (R═H) was accomplishedby hydrolyzing the ester with aqueous sodium hydroxide and thenacidifying the product with hydrochloric acid. For those compounds inwhich R is 2-(2-methoxyethoxy)ethyl, transesterification of the methylester with 2-(2-methoxyethoxy)ethanol in the presence of titanium (IV)isopropoxide was utilized.

Intermediates were prepared according to the following schemata:##STR8##

Thus, a mixture of an appropriately substituted formyl-substitutedphenol and a methyl 2-bromoalkanoate was heated at 70° C. in 2-butanonein the presence of potassium carbonate. Usually the reaction was runovernight, producing the corresponding 2-(substitutedformylphenoxy)alkanoate (IV). This compound was then reduced with sodiummethoxide and sodium borohydride in methanol, yielding the corresponding2-(hydroxymethylphenoxy)alkanoate (V). Reaction of V with thionylchloride in methylene chloride in the presence of a catalytic amount ofpyridine produced the corresponding 2-(chloromethylphenoxy)alkanoate(II). ##STR9##

To prepare compounds of the invention in which Q is4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl, a3-halo-4-fluoronitrobenzene was reacted with hydrazine in isopropanol atreflux, preparing the corresponding 2-halo-4-nitrophenylhydrazine (VI).Reaction of VI with pyruvic acid in ethanol and water produced the2-halo-4-nitrophenylhydrazone of pyruvic acid (VII). Preparation of thetriazolinone ring was accomplished by heating VII withdiphenylphosphoryl azide and triethylamine in toluene at reflux,producing1-(2-halo-4-nitrophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one(VIII). Chlorodifluoromethane was then reacted with VIII and potassiumcarbonate in 1-methyl-2-pyrrolidinone by heating the mixture at 120° C.,producing1-(2-halo-4-nitrophenyl)-4-difluoromethyl-3-methyl-1,2,4-triazol-5(1H)-one(IX). Hydrogenation of IX in ethanol using platinum oxide as catalystproduced1-(4-amino-2-halophenyl)-4,5-dihydro-4-difluoromethyl-3-methyl-1,2,4-triazol-5(1H)-one(X). Preparation of intermediate III (a) was completed by reaction of Xwith sodium nitrite in sulfuric acid and subsequently with copper (II)sulfate in the presence of iron (II) sulfate in a mixture of water andxylenes. ##STR10##

To prepare the tetrahydrophthalimide-substituted intermediate (III(b)),an appropriately substituted 4-aminophenol was refluxed withtetrahydrophthalic anhydride, producing the correspondingN-(4-hydroxy-substituted-phenyl)tetrahydrophthalimide. ##STR11##

An appropriately substituted 4-nitrophenol was heated with methyl iodidein the presence of potassium carbonate in 2-butanone to prepare thecorresponding substituted 4-nitroanisole (XI). Compound XI washydrogenated over platinum oxide, producing a substituted4-methoxyaniline (XII). The reaction of XII with trichloromethylchloroformate prepared the corresponding substituted 4-methoxyphenylisocyanate (XIII). Reaction of this isocyanate with the ethyl ester ofglycine hydrochloride and triethylamine in chloroform yieldedN-(4-methoxy-substituted-phenyl)-N'-ethoxy-carbonylmethylurea (XIV).Sequentially, XIV was reacted with sodium hydride and then with2-iodopropane, yielding ultimately1-(1-methylethyl)-3-(4-methoxy-substituted-phenyl)imidazolidin-2,4-dione(XV). Cleavage of the methoxy group of XV with boron tribromide yieldedintermediate III (c). ##STR12##

An appropriately substituted phenyl isocyanate (XIII(b)) was prepared bythe first three steps of Schema D and then was reacted withtrimethylsilyl azide to prepare the correspondingly substitutedphenyl-substituted tetrazolinone (XVI). After this tetrazolinone wasalkylated in the 4-position with 1-bromo-3-fluoropropane to make the3-fluoropropyl-substituted compound (XVII), the 4-fluorobenzylprotecting group was removed with 49% hydrobromic acid in acetic acid,yielding the desired hydroxy-substituted intermediate (XVIII). ##STR13##

The diazonium salt of 2-fluoro-4-methoxyaniline was prepared usingsodium nitrite and hydrochloric acid and was then reduced in situ withtin(II) chloride to prepare the correspondingly substitutedphenylhydrazine (XIX). Reaction of this hydrazine with ethyl2-cyclohexanonecarboxylate and subsequent heating of the product in thepresence of acetic acid produced a mixture of2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-one (XX)and the 2-fluoro-4-methoxyphenylhydrazone of 2-cyclohexanonecarboxylicacid. This mixture was heated in phosphorus oxychloride, yielding3-chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole (XXI),which was then cleaved with boron tribromide to the desired3-chloro-2-(2-fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydroindazole (XXII).##STR14##

Etherification of 3-fluoro-4-nitrophenol with isopropyl iodide in thepresence of potassium carbonate produced2-fluoro-4-isopropoxynitrobenzene (XI(b)), which was reduced to2-fluoro-4-isopropoxyaniline (XII(b)) with iron in aqueous acetic acid.Malonic acid was reacted with urethane (ethyl carbamate) in phosphorusoxychloride to produce malonyldiurethane (XXIII). The reaction of XII(b)and XXIII was effected by sodium nitrite and hydrochloric acid,producing 2-(4-isopropoxy-2-fluorophenyl)hydrazonomalonyldiurethane(XXIV), which was cyclized with sodium hydroxide to the corresponding2-(substituted phenyl)-1,2,4-triazine-3,5-dion-6-carboxylic acid (XXV).Decarboxylation of XXV with thioglycolic acid and heat yielded XXVIwhich was then methylated at the 4-position with sodium hydride andmethyl iodide producing the corresponding 2-(substitutedphenyl)-4-methyl-1,2,4-triazine-3,5-dione (XXVII). In the final step theisopropyl protecting group was cleaved from the molecule withconcentrated sulfuric acid, producing the desired hydroxy-substitutedintermediate (XXVIII). ##STR15##

Preparation of the mercapto analog of intermediate III(a) started withintermediate X, which was converted to the corresponding diazonium salt.This diazonium compound was immediately reacted with copper (II)chloride and sulfur dioxide in aqueous acetic acid, producing thecorresponding substituted phenylsulfonyl chloride (XXIX). Reduction ofthe sulfonyl chloride moiety to a thiol group was effected using tin(II) chloride in acetic acid, yielding, for example,4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenol(XXX), the desired intermediate. ##STR16##

Unlike the preparation of the other heterocyclic-substituted herbicidalcompounds of this invention, where the final step is the reaction of IIand III to form the herbicide, in the preparation of the compounds inwhich Q is 8-thia-1,6-diazabicyclo 4.3.0!nonane-7-on-9-ylimino II andIII are first reacted to form an intermediate prior to forming theheterocycle. Thus, II was reacted with 3-fluoro-4-nitrophenol in N,N-dimethylformamide in the presence of potassium carbonate, yielding a2-(4-nitrophenoxymethylphenoxy)alkanoate (XXXI). Reduction of XXXI withiron and water in acetic acid produced the corresponding amino compound(XXXII), which was then converted to the isothiocyanate (XXXIII) withthiophosgene and trimethylamine. Perhydropyridazine monohydroiodide andXXXIII were then reacted, forming a2-(4-perhydropyridazin-1-ylthiocarbonylaminophenoxymethylphenoxy!alkanoate(XXXIV). Cyclization of XXXIV using trichloromethyl chloroformate andtriethylamine yielded, for example, methyl 2- 2-4-(8-thia-1,6-diazabicyclo4.3.0!nonane-7-on-9-ylimino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionate(XXXV), the desired herbicidal compound.

Similarly, the compounds in which Q is1-methyl-6-trifluoromethyl-2,4-pyrimidinedione-3-yl may be prepared bythe method of Schema I through the preparation of XXXII. Then XXXII isconverted to the isocyanate with phosgene in place of thiophosgene, andthe isocyanate is reacted with ethyl 3-amino-4,4,4-trifluoro-2-butenoateto yield the desired herbicidal compound.

In this specification "lower alkyl" contains 1 to 6 carbons, preferably1 to 4, "lower alkenyl" or "lower alkynyl" contains 2 to 6 carbons,preferably 2 to 4, "cycloalkyl" contains 3 to 6 carbons, and "halogen"or "halo" means bromine, chlorine, or fluorine, preferably chlorine orfluorine.

The methods for preparing the novel herbicidal compounds of theinvention are exemplified below.

All NMR spectra are reported as proton assignments in ppm in CDCl₃.

EXAMPLE 1

METHYL 2- 2-4-(4-DIFLUOROMETHYL-4,5-DIHYDRO-3-METHYL-1,2,4-TRIAZOL-5(1H)-ON-1-YL)-3-FLUOROPHENOXYMETHYL!-5-METHYLPHENOXY!PROPIONATE(Compound 12)

Step A: 2-Fluoro-4-nitrophenylhydrazone of pyruvic acid

A thick mixture of 21.6 g (0.126 mole) of wet2-fluoro-4-nitrophenylhydrazine in 100 mL of ethanol and 11.27 g (0.128mole) of pyruvic acid in 20 mL of water were mixed. After the reactionmixture had stirred for 20 minutes, it was filtered to yield 15.5 g of ayellow solid, m.p. 210° C. (decomposition). An NMR spectrum of theproduct was consistent with the structure of the2-fluoro-4-nitrophenylhydrazone of pyruvic acid. This reaction wasrepeated to obtain additional product.

Step B:1-(2-Fluoro-4-nitrophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

A mixture of 29.62 g (0.123 mole) of the 2-fluoro-4-nitrophenylhydrazoneof pyruvic acid, 12.45 g (0.123 mole) of triethylamine, and 33.85 g(0.123 mole) of diphenylphosphoryl azide in 200 mL of toluene was heatedslowly to reflux. Heating at reflux was continued for two hours duringwhich this yellow mixture became an orange solution. After cooling toroom temperature, the reaction mixture was extracted with a solution of17.0 g (0.425 mole) of sodium hydroxide in 200 mL of water. The aqueousextract was separated and was almost completely neutralized withconcentrated hydrochloric acid. Just before pH 7 was reached, dry icewas added to the solution, completing the neutralization and causing abrown solid to precipitate. Filtration of this mixture yielded 26.15 gof1-(2-fluoro-4-nitrophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-oneas a brown solid, m.p. 211°-212° C. The NMR spectrum was consistent withthe proposed structure.

Step C:1-(2-Fluoro-4-nitrophenyl)-4-difluoromethyl-4,5-dihydro-1,2,4-triazol-5(1H)-one

A mixture of 5.0 g (0.025 mole) of1-(2-fluoro-4-nitrophenyl)-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-oneand 29.0 g (0.210 mole) of dry, ground potassium carbonate in 200 mL of1-methyl-2-pyrrolidinone was heated at 120° C. for 30 minutes.Chlorodifluoromethane was bubbled into the reaction mixture for fiveminutes. Thin layer chromatography of the reaction mixture revealed thatthe reaction had not gone to completion. Therefore,chlorodifluoromethane was bubbled into the reaction mixture for anadditional three minutes. The reaction mixture was poured over ice andthen was neutralized with concentrated hydrochloric acid. This mixturewas extracted twice with diethyl ether. The combined extracts werewashed with water, dried over anhydrous magnesium sulfate, and filtered.The filtrate was evaporated under reduced pressure, leaving a dark brownsolid residue. This solid was dissolved in 100 mL of acetic acid and 5mL of hydrobromic acid, and this solution was heated at reflux for onehour. This mixture was poured over ice and was then extracted with ethylacetate. This extract was washed twice with water, dried over anhydrousmagnesium sulfate, and filtered. The filtrate was evaporated underreduced pressure, leaving a black oil as a residue. This residue was puton a silica gel column and eluted with methylene chloride/ethyl acetate(97.5/2.5). After the product-containing fractions had been combined,the solvents were evaporated under reduced pressure, leaving 4.6 g of1-(2-fluoro-4-nitrophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-oneas a residue, m.p. 72°-77° C. The NMR spectrum was consistent with theproposed structure.

This reaction was repeated to obtain additional1-(2-fluoro-4-nitrophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-onefor the remainder of the synthesis.

Step D:1-(2-Fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

A mixture of 24.5 g (0.085 mole) of1-(2-fluoro-4-nitrophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-oneand 0.30 g of platinum oxide in 250 mL of absolute ethanol washydrogenated in a Parr hydrogenation apparatus. The calculated amount ofhydrogen required was taken up in 45 minutes. The reaction mixture wasfiltered through a Buchner funnel, and the filtrate was evaporated underreduced pressure, leaving a dark brown solid residue. This residue wasplaced on a silica gel column and eluted with methylene chloride/ethylacetate (75/25). After the product-containing fractions were combined,evaporation of the solvents under reduced pressure yielded 20.1 g of1-(2-fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one.The NMR spectrum was consistent with the proposed structure.

Step E:1-(2-Fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one

A solution of 20.0 g (0.0774 mole) of1-(2-fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-onein 100 mL of concentrated sulfuric acid was cooled to 15°-20° C. Asolution of 5.3 g (0.0774 mole) of sodium nitrite in 20 mL of water wasadded slowly to the sulfuric acid solution while the temperature wasmaintained between 15° C. and 20° C. The dark orange solution wasstirred for an hour at this temperature. The solution was then addedrapidly to a solution of 250 g (1.00 mole) of copper (II) sulfatepentahydrate and 2.0 g (0.0072 mole) of iron (II) sulfate heptahydratein 250 mL of water and 250 mL of mixed xylenes. This two-phase solutionwas heated at reflux for one hour, after which it was cooled and thephases separated. The organic layer was dried over anhydrous magnesiumsulfate and filtered. The filtrate was evaporated under reducedpressure, leaving a brown oil. The aqueous layer was extracted withethyl acetate, and the extract was dried over anhydrous magnesiumsulfate and then filtered. The extract was combined with the brown oilfrom the organic phase, and the solvent was evaporated under reducedpressure, again leaving a brown oil. This brown oil was placed on asilica gel column and eluted with methylene chloride/ethyl acetate(90/10). The product-containing fractions were combined, and the solventwas evaporated under reduced pressure, leaving 12.17 g of1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one,m.p. 112°-114° C. The NMR spectrum was consistent with the proposedstructure.

Step F: Methyl 2-(formyl-5-methylphenoxy)propionate

A mixture of 6.0 g (0.0441 mole) of 4-methylsalicylaldehyde, 7.31 g(0.0529 mole) of potassium carbonate, and 8.62 g (0.0529 mole) of methyl2-bromopropionate in 50 mL of 2-butanone was heated at 70° C. forapproximately seventeen hours. The mixture was then filtered, and thefiltrate was evaporated under reduced pressure, leaving a light yellowoil as a residue. This oil was placed on a silica gel column and elutedfirst with diethyl ether/petroleum ether (25/75) and then with diethylether. After the product-containing fractions were combined and thesolvents evaporated under reduced pressure, 8.2 g of methyl2-(2-formyl-5-methylphenoxy)propionate was recovered as a white solid,m.p. 65°-68° C. The NMR and IR spectra were consistent with the proposedstructure.

Step G: Methyl 2-(2-hydroxymethyl-5-methylphenoxy)propionate

To a solution of 7.89 g (0.0355 mole) of methyl2-(2-formyl-5-methylphenoxy)propionate in 20 mL of methanol, cooled to5° C., was added a solution of 0.10 g (0.0018 mole) of sodium methoxidein 20 mL of methanol. While the temperature was maintained between 0° C.and 5° C., 0.36 g (0.0094 mole) of sodium borohydride was added to thereaction during a period of about 10 minutes. The reaction mixture wasallowed to warm to ambient temperature, where it was stirred for twohours. At the end of this period, the reaction mixture was poured into75 mL of 0.25N hydrochloric acid. This mixture was extracted twice withmethylene chloride. The combined extracts were washed with a saturatedaqueous solution of sodium chloride, dried over anhydrous magnesiumsulfate, and filtered. The filtrate was evaporated under reducedpressure, leaving a colorless oil as a residue. This oil was placed on asilica gel column and eluted first with methylene chloride/ethyl acetate(95/5) and then with the same solvents (90/10). After theproduct-containing fractions were combined and the solvents evaporatedunder reduced pressure, 5.76 g of methyl2-(2-hydroxymethyl-5-methylphenoxy)propionate was isolated as acolorless oil. The NMR and IR spectra were consistent with the proposedstructure.

Step H: Methyl 2-(2-chloromethyl-5-methylphenoxy)propionate

A solution of 2.20 g (0.0098 mole) of methyl2-(2-hydroxymethyl-5-methylphenoxy)propionate in 10 mL of dry methylenechloride was added to a colorless solution of 1.28 g (0.0108 mole) ofthionyl chloride and 5 drops of pyridine in 10 mL of dry methylenechloride during a 10 minute period. This mixture was heated at refluxfor one hour and then poured into 50 mL of water. The phases wereseparated, and the aqueous phase was extracted three times withmethylene chloride. These extracts were combined with the organic phase,which was then washed three times with a saturated aqueous solution ofsodium bicarbonate and once with a saturated aqueous solution of sodiumchloride. The organic phase was then dried over anhydrous magnesiumsulfate, filtered, and the filtrate was evaporated under reducedpressure, leaving a yellow oil as a residue. This oil was placed on asilica gel column and eluted with methylene chloride. After theproduct-containing fractions were combined and the solvent evaporatedunder reduced pressure, 2.06 g of methyl2-(2-chloromethyl-5-methylphenoxy)propionate was recovered as acolorless oil. The NMR spectrum was consistent with the proposedstructure.

Step I: Methyl 2- 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!propionate

A mixture of 0.50 g (0.0019 mole) of1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one,0.39 g (0.0028 mole) of anhydrous potassium carbonate, and 0.92 g(0.0038 mole) of methyl 2-(2-chloromethyl-5-methylphenoxy)propionate in20 mL of N,N-dimethylformamide was heated at 90° C. for approximately 17hours. At the end of this period the mixture was poured over ice, andthe resulting mixture was extracted with ethyl acetate. The extract waswashed with water, dried over anhydrous magnesium sulfate, and filtered.The filtrate was evaporated under reduced pressure, leaving an orangeoil as a residue. This oil was placed on a silica gel column and elutedfirst with methylene chloride and then with methylene chloride/ethylacetate (97.5/2.5). After the product-containing fractions were combinedand the solvents evaporated under reduced pressure, 0.82 g of 2- 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!propionatewas recovered as a yellow oil. The NMR and IR spectra were consistentwith the proposed structure. NMR: 1.60 (d, 3H, J_(HH) =8.0 Hz); 2.30 (s,3H); 2.44 (s, 3H); 3.76 (s, 3H); 4.84 (q, 1H, J_(HH) =8.0 Hz); 5.16 (dd,2H, J_(HH) =10.0 Hz); 6.56 (s, 1H); 6.78-7.32 (m, 6H).

EXAMPLE 2

METHYL 2- 2-3-FLUORO-4-(3,4,5,6-TETRAHYDRO-1-PHTHALIMIDYL)PHENOXYMETHYL!-5-CHLOROPHENOXY!PROPIONATE(Compound 27)

Step A: Synthesis of 4-amino-3-fluorophenol

To a mixture of 10.0 g (0.0640 mole) of 3-fluoro-4-nitrophenol in 100 mLof acetic acid and 10 mL of water heated to 50° C. was added 10.0 g(0.179 mole) of iron powder in small portions during a 35 minute period.The stirred reaction mixture was heated at 50° C. for an additionalthree hours, after which it was cooled and filtered. The filtrate wasused in Step B without further purification.

Step B: N-(2-fluoro-4-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide

The filtrate from Step A was mixed with 9.74 g (0.0640 mole) of3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated atreflux for approximately 64 hours. At the end of this period, the darkbrown solution was poured over ice and extracted in succession withethyl acetate and diethyl ether. The extracts were combined, washed withwater, dried over anhydrous magnesium sulfate, and filtered. Thesolvents were evaporated under reduced pressure from the filtrate,leaving a dark brown oil as residue. This was placed on a silica gelcolumn and eluted with methylene chloride/ethyl acetate (95/5). Afterthe product-containing fractions were combined and the solventsevaporated under reduced pressure, 14.71 g ofN-(2-fluoro-4-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide was recoveredas an orange solid, m.p. 132°-136° C. The NMR spectrum was consistentwith the proposed structure.

Step C: Methyl 2-(5-chloro-2-formylphenoxy)propionate

A mixture of 22.0 g (0.141 mole) of 4-chlorosalicylaldehyde, 30 g (0.22mole) of anhydrous potassium carbonate, and 30.0 g (0.184 mole) ofmethyl 2-bromopropionate in 120 mL of N,N-dimethylformamide was heatedat 80° C. for approximately 17 hours. At the end of that period, thereaction mixture was poured over ice and extracted successively withdiethyl ether and ethyl acetate. The combined extracts were washed withwater, dried over anhydrous magnesium sulfate, and filtered. Thesolvents were then evaporated under reduced pressure, leaving a residueweighing 20 g. This residue was purified by placing it on a silica gelcolumn and eluting with diethyl ether/petroleum ether (25/75). After theproduct-containing fractions were combined and the solvents evaporatedunder reduced pressure, 6.23 g of methyl2-(5-chloro-2-formylphenoxy)propionate was isolated as a yellow liquid.Similarly, other fractions were combined and evaporated, yielding 1.69 gof methyl 2-(3-chloro-2-formylphenoxy)propionate as a yellow liquid. TheNMR spectra of both compounds were consistent with proposed structure ofeach. This reaction was repeated several times.

Step D: Methyl 2-(5-chloro-2-hydroxymethylphenoxy)propionate

To a solution of 0.10 g (0.018 mole) of sodium methoxide in 20 mL ofmethanol that had been cooled to 5° C. was added a solution of 8.0 g ofmethyl 2-(5-chloro-2-formylphenoxy)propionate in 20 mL of methanol.While the temperature was maintained between 0° C. and 5° C. to thismixture was added 0.50 g (0.013 mole) of sodium borohydride. Thisaddition required 10 minutes, during which gas was evolved. The yellowsolution was allowed to warm up to room temperature, where it wasstirred for four hours. At the end of this period the reaction mixturewas poured into 100 mL of 0.25N hydrochloric acid. This mixture wasextracted with methylene chloride. The extract was washed with asaturated aqueous solution of sodium chloride, dried over anhydrousmagnesium sulfate, and filtered. The filtrate was evaporated underreduced pressure, leaving a yellow oil as a residue. This oil was placedon a silica gel column and eluted with methylene chloride/ethyl acetate(95/5). After the product-containing fractions were combined and thesolvents evaporated under reduced pressure, 4.42 g of methyl2-(5-chloro-2-hydroxymethylphenoxy)propionate was isolated as an orangeoil, which subsequently solidified, m.p. 51°-52° C.

Step E: Methyl 2-(2-chloromethyl-5-chlorophenoxy)propionate

By the method of Example 1, Step H, 1.0 g (0.0038 mole) of methyl2-(5-chloro-2-hydroxymethylphenoxy)propionate and 0.5 g (0.0042 mole) ofthionyl chloride were reacted in 20 mL of methylene chloride. Afterpurification, 0.88 g of methyl2-(2-chloromethyl-5-chlorophenoxy)propionate was isolated as a yellowliquid. The NMR spectrum was consistent with the proposed structure.

Step F: Methyl 2- 2-3-fluoro-4-(3,4,5,6-tetrahydro-1-phthalimidyl)phenoxymethyl!-5-chlorophenoxy!propionate

By the method of Example 1, Step I, 0.50 g (0.0019 mole) ofN-(2-fluoro-4-hydroxyphenyl)-3,4,5,6-tetrahydrophthalimide, 0.88g.(0.0034 mole) of methyl 2-(2-chloromethyl-5-chlorophenoxy)propionate,and 0.39 g (0.0028 mole) of potassium carbonate were reacted in 20 mL of2-butanone. After purification, 0.58 g of methyl 2- 2-3-fluoro-4-(3,4,5,6-tetrahydro-1-phthalimidyl)phenoxymethyl!-5-chlorophenoxy!propionatewas isolated as a yellow solid, m.p. 110°-112° C. The NMR and IR spectrawere consistent with the proposed structure. NMR: 1.64 (d, 3H, J_(HH) =8Hz); 1.80 (bs, 4H); 2.40 (bs, 4H); 3,78 (s, 3H); 4.84 (q, 1H, J_(HH)=8.0 Hz); 5.14 (s, 2H); 6.78-7.38 (m, 6H).

EXAMPLE 3

METHYL 2- 2- 3-FLUORO-4-1-(1-METHYLETHYL)-IMIDAZOLIDIN-2,4-DION-3-YL!PHENOXYMETHYL!-5-CHLOROPHENOXY!PROPIONATE(Compound 44)

Step A: 2-Fluoro-4-methoxyphenyl isocyanate

To a solution of 13.75 g (0.0967 mole) of 2-fluoro-4-methoxyaniline in120 mL of toluene was slowly added over a period of 30 minutes asolution of 19.13 g (0.0967 mole) of trichloromethyl chloroformate in 30mL of toluene. During the addition the temperature rose to 35° C. Thereaction mixture was stirred without external heating for 30 minutes andthen heated at reflux for approximately 17 hours. At the end of thistime all of the solvent was removed by distillation, leaving2-fluoro-4-methoxyphenyl isocyanate as a purple liquid, which was usedimmediately in Step B.

Step B: N-(2-Fluoro-4-methoxyphenyl)-N'-ethoxycarbonylmethylurea

A solution of 2-fluoro-4-methoxyphenyl isocyanate (assumed to weigh 16.2g (0.0967 mole) from Step A), 13.50 g (0.0967 mole) of glycine ethylester hydrochloride in 100 mL of chloroform was placed in a flask, and asolution of 9.28 g (0.0967 mole) of triethylamine in 25 mL of chloroformwas added during a 20 minute period. The temperature rose to 38° C.during the addition. Upon completion of addition, the reaction mixturewas stirred at ambient temperature for three hours and then poured intoa mixture of heptane and water. By filtration,N-2(2-fluoro-4-methoxyphenyl)-N'-ethoxycarbonylmethylurea was isolatedfrom this mixture as a purple solid, m.p. 158°-159° C. The organic phaseof the filtrate was separated, dried over anhydrous magnesium sulfate,and filtered. The solvent was evaporated from the filtrate under reducedpressure, leaving a purple solid as residue. This solid wasrecrystallized from ethyl acetate/petroleum ether. The recrystallizedsolid was placed on a silica gel column and eluted sequentially withmethylene chloride, methylene chloride/ethyl acetate (90/10), andfinally methylene chloride/ethyl acetate (75/25). After theproduct-containing fractions were combined and the solvents evaporatedunder reduced pressure, additionalN-(2-fluoro-4-methoxyphenyl)-N'-ethoxycarbonylmethylurea was isolated asa purple solid, m.p. 158°-159° C. The total yield ofN-(2-fluoro-4-methoxyphenyl-N'-ethoxycarbonylmethylurea weighed 17.33 g.The NMR spectra of these solids were consistent with the proposedstructure.

Step C:1-(1-Methylethyl)-3-(2-fluoro-4-methoxyphenyl)imidazolidin-2,4-dione

A solution of 17.02 g (0.0630 mole) ofN-(2-fluoro-4-methoxyphenyl-N'-ethoxycarbonylmethylurea in 50 mL ofN,N-dimethylformamide was added dropwise to a suspension of 2.65 g(0.0662 mole) of sodium hydride in 30 mL of N,N-dimethylformamide duringa 20 minute period. Gas evolution and a slight rise in temperatureoccurred during the addition. This mixture was stirred at roomtemperature for 45 minutes, by which time it had become a homogeneoussolution. To this solution was added dropwise, over a period of 15minutes, a solution of 21.42 g (0.126 mole) of 2-iodopropane in 10 mL ofN,N-dimethylformamide. The temperature rose to 38° C. during theaddition period. This reaction mixture was stirred for approximately 65hours, then poured over ice and extracted with diethyl ether. Theextract was washed twice with water, dried over anhydrous magnesiumsulfate, and filtered. The filtrate was evaporated under reducedpressure, leaving an orange oil as a residue. This oil was placed on asilica gel column and eluted sequentially with 97.5/2.5 and 95/5mixtures of methylene chloride and ethyl acetate. After theproduct-containing fractions were combined and the solvents evaporatedunder reduced pressure, 5.85 g of1-(1-methylethyl-3-(2-fluoro-4-methoxyphenyl)imidazolidin-2,4-dione wasisolated as an orange solid, m.p. 88°-90° C.

Step D:1-(1-methylethyl)-3-(2-fluoro-4-hydroxyphenyl)imidazolidin-2,4-dione

A 1M methylene chloride solution of boron tribromide (41.6 ml, 0.0416mole) was cooled to -20° C. While this temperature was maintained, asolution of 5.55 g (0.0208 mole) of1-(1-methylethyl)-3-(2-fluoro-4-methoxyphenyl)imidazolidin-2,4-dione in25 mL of methylene chloride was added to the reaction during an eightminute period. The reaction mixture was allowed to warm to roomtemperature, where it was stirred for approximately 17 hours. At the endof this time the reaction was poured over ice, and the resultingtwo-phase mixture was filtered. The organic phase was separated, driedover anhydrous magnesium sulfate, and filtered. The filtrate wasevaporated under reduced pressure, leaving a black solid as a residue.This solid was recrystallized from ethyl acetate/petroleum ether, toyield 3.25 g of1-(1-methylethyl)-3-(2-fluoro-4-hydroxyphenyl)imidazolidin-2,4-dione asa tan solid, m.p. 190°-192° C. The NMR and IR spectra were consistentwith the proposed structure.

Step E: Methyl 2- 2- 3-fluoro-4-1-(1-methylethyl)imidazolidin-2,4-dion-3-yl!phenoxymethyl!-5-chlorophenoxy!propionate

By the method of Example 1, Step I, 0.60 g (0.0024 mole) of1-(1-methylethyl)-3-(2-fluoro-4-hydroxyphenyl)imidazolidin-2,4-dione,1.24 g (0.0048 mole) of methyl2-(2-chloromethyl-5-chlorophenoxy)propionate (Example 2, Step E), and0.5 g (0.0036 mole) of potassium carbonate were reacted in 25 mL of2-butanone. After purification, 1.04 g of methyl 2- 2- 3-fluoro-41-(1-methylethyl)imidazolidin-2,4-dion-3-yl!phenoxymethyl!-5-chlorophenoxy!propionatewas isolated as a yellow oil. The NMR and IR spectra were consistentwith the proposed structure. NMR: 1.24 (d, 6H, J_(HH) =8 Hz); 1.64 (d,3H, J_(HH) =8 Hz); 3.68 (s, 3H); 3.96 (s, 1H); 4.44 (septet, 1H, J_(HH)=8.0 Hz); 5.04 (q, 1H, J_(HH) =8.0 Hz); 5.24 (s, 2H); 6.80-7.34 (m, 5H).

EXAMPLE 4

METHYL 2- 2- 4-1,4-DIHYDRO-4-(3-FLUOROPROPYL)-5H-TETRAZOL-5-ON-1-YL!-3-FLUOROPHENOXYMETHYL!-5-METHYLPHENOXY!PROPIONATE(Compound 64)

Step A: 4-Fluorophenylmethyl 3-fluoro-4-nitrophenyl ether

A stirred mixture of 10.0 g (0.063 mole) of 3-fluoro-4-nitrophenol, 17.0g (0.090 mole) of 4-fluorophenylmethyl chloride, and 12.42 g (0.690mole) of anhydrous potassium carbonate in 80 mL of methyl ethyl ketonewas heated at 70° C. for approximately 17 hours. The reaction mixturewas then cooled and filtered and the filtrate evaporated under reducedpressure, leaving 13.10 g of 4-fluorophenylmethyl 3-fluoro-4-nitrophenylether as a solid; m.p. 90°-91° C.

Step B: 4-Fluorophenylmethyl 4-amino-3-fluorophenyl ether

A solution of 11.0 g (0.041 mole) of 4-fluorophenylmethyl3-fluoro-4-nitrophenyl ether in 100 mL of glacial acetic acid and 10 mLof water was heated to 50° C. To this hot solution was added 10.0 g(0.18 mole) of powdered iron. The reaction mixture was allowed to coolto ambient temperature, where it stirred for an additional hour. Thereaction mixture was filtered through a bed of Celite® filter aid, andthe Celite bed was washed in succession with ethyl acetate and 200 mL ofwater. The washes and the filtrate were combined, and the organic phasewas separated. The organic phase was dried with anhydrous magnesiumsulfate, filtered, and the solvent was evaporated under reducedpressure, leaving a dark oil as a residue. This oil was placed on asilica gel column and eluted with methylene chloride. Theproduct-containing fractions were combined and the solvent evaporatedunder reduced pressure, leaving 6.8 g of 4-fluorophenylmethyl4-amino-3-fluorophenyl ether as a solid, m.p. 42°-43° C.

Step C: 4-(4-Fluorophenylmethoxy)-2-fluorophenyl isocyanate

To a solution of 6.50 g (0.0276 mole) of 4-fluorophenylmethyl4-amino-3-fluorophenyl ether in toluene, stirring at room temperature,was slowly added 3.95 g (0.020 mole) of trichloromethyl chloroformate.During the addition a thick precipitate formed. Upon completion ofaddition, the reaction mixture was stirred for one hour at roomtemperature and then at reflux for approximately seventeen hours. Thetoluene was removed by distillation, leaving 7.10 g of4-(4-fluorophenylmethoxy)-2-fluorophenyl isocyanate.

Step D: 1-4-(4-Fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-5H-tetrazol-5-one

A mixture of 7.10 g (0.027 mole) of4-(4-fluorophenylmethoxy)-2-fluorophenyl isocyanate and 7.0 g (0.060mole) of trimethylsilyl azide was heated at reflux for approximatelyseventeen hours. The solution was then allowed to cool to roomtemperature before being poured over ice. A solid formed and wasrecovered by filtration. The solid was dried, leaving 8.08 g of 1-4-(4-fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-5H-tetrazol-5-one,m.p. 171°-172° C.

Step E: 1-4-(4-Fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one

A mixture of 7.0 g (0.023 mole) of 1-4-(4-fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-5H-tetrazol-5-one,4.23 g (0.030 mole) of 1-bromo-3-fluoropropane, and 4.14 g (0.030 mole)of anhydrous potassium carbonate in 60 mL of N,N-dimethylformamide washeated at 70° C. for approximately seventeen hours. The mixture wasallowed to cool to room temperature before being poured over ice. Thesolid that formed was removed by filtration and dried. This solid wasthen placed on a silica gel column and eluted with with methylenechloride. The product-containing fractions were combined and thesolvents evaporated under reduced pressure, leaving 6.35 g of 1-4-(4-fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one,m.p. 86°-88° C.

Step F:1-(2-Fluoro-4-hydroxyphenyl)-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-one

To a solution of 5.60 g (0.0153 mole) of 1-4-(4-fluorophenylmethoxy)-2-fluorophenyl!-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-onein 60 mL of glacial acetic acid was added 5 mL of 49% hydrobromic acid.This mixture was heated at reflux for 90 minutes, after which it wascooled to room temperature. The reaction mixture was then poured overice, and the resulting aqueous solution was extracted with diethylether. The combined extract was dried over magnesium sulfate, filtered,and the solvent was evaporated under reduced pressure, leaving 4.35 g of1-(2-fluoro-4-hydroxyphenyl)-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-oneas a residue.

Step G: Methyl 2- 2- 4-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-on-1-yl!-3-fluorophenoxymethyl!-5-methylphenoxy!propionate

By the method Example 1, Step I, 0.85 g (0.0033 mole) of1-(2-fluoro-4-hydroxyphenyl)-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-oneand 1.21 g (0.0050 mole) of methyl2-(2-chloromethyl-5-methylphenoxy)propionate (Example 1, Step H) werereacted in the presence of 0.70 g (0.0050 mole) of anhydrous potassiumcarbonate in 60 mL of N,N-dimethylformamide, yielding 0.42 g of methyl2- 2- 4-1,4-dihydro-4-(3-fluoropropyl)-5H-tetrazol-5-on-1-yl!-3-fluorophenoxymethyl!-5-methylphenoxy!propionateas an oil. The NMR spectrum was consistent with the proposed structure.NMR: 1.64 (d, 3H, J_(HH) =8 Hz); 2.2-2.4 (m, 2H); 2,32 (s, 3H); 3.72 (s,3H); 4.18 (t, 2H, J_(HH) =8 Hz); 4.50-4.64 (dt, 2H, J_(HH) =8 Hz, J_(HF)=45 Hz); 4.84 (q, 1H, J_(HH) =8 Hz), 5.20 (q, 2H, J_(HH) =8 Hz);6.58-7.40 (m, 6H).

EXAMPLE 5

METHYL 2- 2-4-(3-CHLORO-4,5,6,7-TETRAHYDROINDAZOL-2-YL)-3-FLUOROPHENOXYMETHYL!-5-CHLOROPHENOXY!PROPIONATE(Compound 66)

Step A: 2-Fluoro-4-methoxyphenylhydrazine

With vigorous stirring, 9.15 g (0.065 mole) of 2-fluoro-4-methoxyanilinewas added to 60 mL of concentrated hydrochloric acid that had beencooled to -10° C. A solution of 4.83 g (0.070 mole) of sodium nitrite in30 mL of water was slowly added dropwise, while the temperature was keptat or below -10° C. Upon completion of addition, the reaction mixturewas stirred at -10° C. for one hour, after which 33.85 (0.150 mole) oftin(II) chloride dihydrate in 50 mL of concentrated hydrochloric acidwas added slowly, dropwise, while the temperature was kept below -5° C.After the reaction mixture had stirred for one hour as it warmed toambient temperature, the crude product was filtered from the mixture anddissolved in 250 mL of water. This solution was made basic with 4Nsodium hydroxide and extracted with methylene chloride. The combinedextracts were dried over anhydrous sodium sulfate and filtered. Thefiltrate was placed on a silica gel column and eluted with methylenechloride to remove colored impurities and then with ethyl acetate toobtain the desired product. The solvent was evaporated under reducedpressure to yield 6.30 g of 2-fluoro-4-methoxyphenylhydrazine. The NMRspectrum was consistent with the proposed structure.

Step B: 2-(2-Fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-one

To a solution of 6.28 g (0.040 mole) of2-fluoro-4-methoxyphenylhydrazine in 200 mL of toluene was added withstirring 6.82 g (0.040 mole) of ethyl 2-cyclohexanonecarboxylate. Thismixture was heated at reflux under a nitrogen atmosphere while water wasremoved with a Dean-Stark trap. When all water had been removed, thereaction mixture was cooled, and the solvent was evaporated underreduced pressure, leaving a residue which was then dissolved in aceticacid. This solution was heated at reflux for approximately sixteenhours, after which the solvent was evaporated under reduced pressure,leaving a residue. This residue was dissolved in toluene, which was alsoevaporated under reduced pressure. The residue was dissolved in ethylacetate and placed on a silica gel column and eluted with ethyl acetate.An attempt to crystallize the product by dissolving it in diethyl etherafter the ethyl acetate had been evaporated was unsuccessful. After thesolvent had been evaporated from this product, it was again heated atreflux in acetic acid for 24 hours and allowed to cool to roomtemperature, where the solution stirred for an additional 48 hours. Thesolvent was evaporated under reduced pressure, leaving a residueweighing 4.32 g. Two additional fractions weighing 0.80 g and 2.75 g hadbeen recovered by extracting the reaction mixture before the solvent wasevaporated. The NMR spectrum of the residue showed it to be a mixture of2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazol-3-one and the2-fluoro-4-methoxyphenylhydrazone of 2-cyclohexanonecarboxylic acid.

Step C:3-Chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydro-1H-indazole

The 4.32 g residue from Step B was mixed at ambient temperature with5.37 g (0.035 mole) of phosphorus oxychloride until complete dissolutionoccurred. At this point the reaction mixture was heated at reflux undernitrogen for one hour. The phosphorus oxychloride was evaporated fromthe reaction mixture under reduced pressure, leaving a residue weighing1.50 g. This residue, together with a similar residue weighing 0.30 gfrom an earlier experiment, was then was placed on a silica gel columnand eluted with hexane/ethyl acetate (4:1). After the product-containingfractions were combined and the solvents evaporated under reducedpressure, 0.50 g of3-chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole wasisolated. The NMR was consistent with the proposed structure.

Step D: 3-Chloro-2-(2-fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydroindazole

A 1N solution of boron tribromide in methylene chloride (18.0 mL, 0.018mole) was diluted with 17 mL of methylene chloride and was then cooledto below -10° C. under a nitrogen atmosphere. A solution of3-chloro-2-(2-fluoro-4-methoxyphenyl)-4,5,6,7-tetrahydroindazole in 25mL of methylene chloride was added dropwise at a rate to maintain thetemperature below -10° C. Upon completion of addition, the reactionmixture was allowed to warm to ambient temperature at which it stirredfor sixteen hours. The mixture was then poured into ice-water, and theresulting mixture was stirred for 30 minutes. This mixture was filtered,and the filtrate was passed through a short column of silica gel. Theorganic phase was separated, dried with anhydrous sodium sulfate, andfiltered. The solvent was evaporated from the filtrate under reducedpressure, leaving 0.60 g of3-chloro-2-(2-fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydroindazole as anearly white solid, m.p. 214°-216° C. The NMR and IR spectra wereconsistent with the proposed structure.

Step E: Methyl 2- 2-4-(3-chloro-4,5,6,7-tetrahydroindazol-2-yl)-3-fluorophenoxymethyl!-5-chlorophenoxy!propionate

By the method of Example 1, Step I, 0.49 g (0.0016 mole) of3-chloro-2-(2-fluoro-4-hydroxyphenyl)-4,5,6,7-tetrahydroindazole and0.52 g (0.002 mole) of methyl2-(2-chloromethyl-5-chlorophenoxy)propionate (Example 2, Step E) werereacted in the presence of 0.41 g (0.003 mole) of anhydrous potassiumcarbonate in 30 mL of N,N-dimethylformamide, yielding 0.64 g of methyl2- 2-4-(3-chloro-4,5,6,7-tetrahydroindazol-2-yl)-3-fluorophenoxymethyl!-5-chlorophenoxy!propionateas a syrup. The NMR and IR spectra were consistent with the proposedstructure. NMR: 1.64 (d, 3H, J_(HH) =8.0 Hz); 1.82 (m, 4H); 2.50 (t, 2H,J_(HH) =4.0 Hz); 2.68 (t, 2H, J_(HH) =4.0 Hz); 3.76 (s, 3H); 4.82 (q,1H, J_(HH) =8 Hz); 5.18 (s, 2H,); 6.7.8-7.40 (m, 6H).

EXAMPLE 6

METHYL 2- 2-4-(4-METHYL-1,2,4-TRIAZINE-3,5-DION-2-YL)-3-FLUOROPHENOXYMETHYL!-5-METHYLPHENOXY!PROPIONATE(Compound 70)

Step A: 4-Isopropoxy-2-fluoroaniline

A stirred flask containing 350 mL of acetic acid was heated to 80°-85°C. under a nitrogen atmosphere. To this flask was added 39.10 g (0.700mole) of powdered iron, and this mixture was stirred for one hour. Asolution of 4-isopropoxy-2-fluoronitrobenzene in 250 mL was added to themixture dropwise. Upon completion of addition, the reaction mixture washeated at 80°-85° C. for one hour. After being cooled below 40° C., themixture was filtered, and the solvent was evaporated under reducedpressure, leaving a residue. This residue was dissolved in a mixture ofwater and diethyl ether. The organic layer was separated and was washedin succession with saturated aqueous solutions of sodium bicarbonate andsodium chloride. It was then dried over anhydrous magnesium sulfate,filtered through a short column of silica gel, and the solvent wasevaporated under reduced pressure, leaving an impure residue whichcontained significant amounts of acetamide in addition to the desiredproduct. This residue was suspended in 500 mL of 2N hydrochloric acidfor one hour. The hydrochloric acid mixture was then extracted withdiethyl ether, and the two phases were separated. Aqueous sodiumhydroxide solution was added to the aqueous hydrochloride solution untilit was basic. This basic solution was extracted with diethyl ether, andthe extract was dried over anhydrous magnesium sulfate and filtered.After evaporation of the solvent under reduced pressure, the residue wasrecrystallized from diethyl ether/petroleum ether to yield 16.90 g of4-isopropoxy-2-fluoroaniline as an oil which darkened on standing. TheNMR spectrum was consistent with the proposed structure.

Step B: Malonyldiurethane

With a mortar and pestle 10.40 g (0.100 mole) of malonic acid and 18.00g (0.210 mole) of ethyl carbamate were ground to a fine powder. Thispowder was placed in a flask, and 16.0 mL (0.167 mole) of phosphorusoxychloride was added. This mixture was heated at 80° C. until theevolution of gas ceased. After this reaction mixture had cooled toambient temperature, 210 mL of water was added. When the stiff glassymixture became fluid, it was extracted with ethyl acetate. The combinedextracts were washed in succession with saturated aqueous solutions ofsodium bicarbonate and sodium chloride and were then dried overanhydrous magnesium sulfate and filtered. The solution was filteredthrough a short column of silica gel, which was eluted with ethylacetate. The solvent was then evaporated under reduced pressure, leavinga crystalline mass of malonyldiurethane weighing 10.62 g. The NMRspectrum was consistent with the proposed structure.

Step C: 2-(4-Isopropoxy-2-fluorophenyl)hydrazonomalonyldiurethane

A mixture of 5.92 g (0.035 mole) of 4-isopropoxy-2-fluoroaniline, 10.60g (0.043 mole) of malonyldiurethane, and 41.02 g (0.500 mole) of sodiumacetate was suspended in 1000 mL of water with vigorous stirring. Tothis suspension was added 25 mL of 12N hydrochloric acid. The reactionmixture was cooled to 10° C., and, while this temperature wasmaintained, a solution of 2.42 g (0.035 mole) of sodium nitrite in 25 mLof water was slowly added. The reaction mixture was allowed to warmslowly to room temperature where it was stirred under a nitrogenatmosphere for approximately 16 hours. During this period a yellow solidformed and precipitated out. The mixture was filtered, and the yellowsolid was washed in succession with water and diethyl ether. After beingdried, 9.20 g of2-(4-isopropoxy-2-fluorophenyl)hydrazonomalonyldiurethane was isolatedas a yellow solid. The NMR and IR spectra were consistent with theproposed structure.

Step D:2-(4-Isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dion-6-carboxylicacid

To a stirred solution of 8.94 g (0.021 mole) of2-(4-isopropoxy-2-fluorophenyl)hydrazonomalonyldiurethane in 125 mL ofethanol and 125 mL of tetrahydrofuran was added 75 mL (0.134 mole) of10% aqueous potassium hydroxide, initially forming a precipitate, whichsubsequently dissolved. After this mixture was stirred for 30 minutes atambient temperature, 30 mL of 11.7N hydrochloric acid was addedcarefully with stirring. The tetrahydrofuran was evaporated underreduced pressure, and the residue was then extracted with ethyl acetate.The combined extracts were treated with decolorizing charcoal, driedover anhydrous magnesium sulfate, and filtered through a short column ofsilica gel, which was eluted with ethyl acetate. The solvent wasevaporated from the filtrate, yielding 4.70 g of2-(4-isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dion-6-carboxylicacid as an amorphous foam. The NMR spectrum was consistent with theproposed structure.

Step E: 2-(4-Isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dione

A solution of 4.70 g (0.0152 mole) of2-(4-isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dion-6-carboxylicacid in 5 mL of mercaptoacetic acid was heated at 140°-145° C. for twohours under a nitrogen atmosphere. After this mixture had cooled, it waspoured into 250 mL of a saturated aqueous solution of sodium bicarbonatewith vigorous stirring. An equal volume of ethyl acetate was added tothis mixture, and the resulting layers were separated. The organic layerwas washed twice with 150 mL of a saturated aqueous solution of sodiumbicarbonate and once with 150 mL of a saturated aqueous solution ofsodium chloride. The organic solution was then dried over anhydrousmagnesium sulfate and filtered. The solvent was evaporated under reducedpressure, leaving a syrup which slowly crystallized to a yellow-orangesolid upon standing. This solid was recrystallized from ethylacetate/petroleum ether (1:1), yielding 0.60 g of2-(4-isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dione as a yellowsolid. The NMR was consistent with the proposed structure. This reactionwas repeated to obtain additional material for subsequent reactions.

Step F:2-(4-Isopropoxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione

A solution of 3.25 g (0.0123 mole) of2-(4-isopropoxy-2-fluorophenyl)-1,2,4-triazine-3,5-dione in 30 mL ofN,N-dimethylformamide was added to a suspension of 0.50 g (0.0125 mole)of sodium hydride in 30 mL of N,N-dimethylformamide at ambienttemperature. When gas evolution had ceased, 3.55 g (0.025 mole) ofiodomethane was added in one portion. This mixture was stirred for onehour without heating and was then poured into 300 mL of dilutehydrochloric acid. The resulting mixture was extracted several timeswith diethyl ether, and the extracts were combined. The ether extractwas washed in succession with water and a saturated aqueous solution ofsodium chloride. It was then dried over anhydrous magnesium sulfate andfiltered through a short column of silica gel. The solvent wasevaporated under reduced pressure, leaving 2.80 g of2-(4-isopropoxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione as asyrup. The NMR was consistent with the proposed structure.

Step G: 2-(4-Hydroxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5,-dione

Concentrated sulfuric acid (5 mL) that had been cooled to 0°-5° C. wasmixed with 2.80 g (0.010 mole) of2-(4-isopropoxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione thathad been cooled to 0° C. The mixture was maintained at 9° C. for tenminutes, during which time it became homogeneous. The mixture was thenpoured into ice-water, and the resulting mixture was extracted withethyl acetate. The extract was washed in succession with a saturatedaqueous solution of sodium bicarbonate and a saturated aqueous solutionof sodium chloride. The extract was dried over anhydrous magnesiumsulfate and filtered. The solvent was evaporated from the filtrate underreduced pressure, leaving a residue. This residue was placed on a columnof silica gel and eluted with ethyl acetate/hexane (1:1). After theproduct-containing fractions were combined and the solvents evaporatedunder reduced pressure, 1.38 g of2-(4-hydroxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione wasrecovered as a stiff syrup. The NMR was consistent with the proposedstructure.

Step H: Methyl 2- 2-4-(4-methyl-1,2,4-triazine-3,5-dion-2-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!propionate

By the method of Example 1, Step I, 0.47 g (0.002 mole) of2-(4-hydroxy-2-fluorophenyl)-4-methyl-1,2,4-triazine-3,5-dione and 0.73g (0.003 mole) of methyl 2-(2-chloromethyl-5-methylphenoxy)propionatewere reacted in the presence of 0.4.1 g (0.003 mole) of anhydrouspotassium carbonate in 30 mL of N,N-dimethylformamide, yielding 0.70 gof methyl 2- 2-4-(4-methyl-1,2,4-triazine-3,5-dion-2-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!propionateas a syrup. The IR and NMR spectra were consistent with the proposedstructure. NMR: 1.60 (d, 3H, J_(HH) =8.0 Hz); 2.30 (s, 3H); 3.40 (s,3H); 3.78 (s, 3H); 4.84 (q, 1H, J_(HH) =8.0 Hz); 5.18 (dd, 2H, J_(HH)=10 Hz); 6.58 (s, 1H); 6.8-7.3 (m, 5H); 7.54 (s, 1H).

EXAMPLE 7

METHYL 2- 2-4-(4-DIFLUOROMETHYL-4,5-DIHYDRO-3-METHYL-1,2,4-TRIAZOL-5(1H)-ON-1-YL)-3-FLUOROPHENYLTHIOMETHYL!-5-CHLOROPHENOXY!PROPIONATE(Compound 72)

Step A4-(4-Difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylsulfonylchloride

A mixture of 2.02 g (0.0078 mole) of1-(2-fluoro-4-aminophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4,-triazol-5(1H)-one(Example 1, Step D) in 20 mL of hydrochloric acid was cooled to 0° C.,and 0.55 g (0.0084 mole) of sodium nitrite in 5 mL of water was addedslowly while the temperature was held at 0°-5° C. The yellow solutionwas then stirred at room temperature for two hours. Meanwhile a solutionof 1.08 g (0.0080 mole) of copper(II) chloride in 5 mL of water and 20mL of acetic was prepared, and sulfur dioxide was bubbled through thissolution until it was saturated, a period of ten minutes. After havingbeen stirred for two hours, the yellow solution was added slowly to thesolution saturated with sulfur dioxide. The mixture turned green, and ayellow precipitate formed. During the addition, the temperature rose to32° C. The reaction mixture was stirred for an hour at room temperatureand then poured over ice. The pale yellow solid that formed was isolatedby filtration, yielding 1,86 g of4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylsulfonylchloride. The NMR spectrum was consistent with the proposed structure.This reaction was repeated to obtain additional product for subsequentreactions.

Step B4-(4-Difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenol

Gaseous hydrogen chloride was bubbled into a mixture of 3.29 g (0.0146mole) of tin(II) chloride in 40 mL of acetic acid for about fiveminutes, causing it to become a clear solution. This solution was thenheated to 85° C., and a hot solution of 1.66 g (0.00485 mole) of4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylsulfonylchloride was added to the first solution. This reaction mixture washeated at 85° C. for 45 minutes. After cooling to room temperature, theresulting yellow solution was poured into 120 mL of hydrochloric acid.To this mixture was added 100 mL of a saturated aqueous solution ofsodium chloride, and the resulting mixture was extracted with ethylacetate, but the layers did not separate. The addition of a saturatedaqueous solution of sodium chloride did effect a partial separation. Theaqueous layer was extracted two more times with ethyl acetate, and allextracts were combined. After evaporation of the solvent under reducedpressure, the residue retained an odor of hydrochloric acid. Water wasadded to the residue, and this mixture was extracted three times withethyl acetate. The combined extracts were washed with water, dried overanhydrous magnesium sulfate, and filtered. Following evaporation of thesolvent under reduced pressure, the yellow residue that remained wasdried under vacuum. This dried residue was placed on a column of silicagel and eluted with methylene chloride/ethyl acetate (2:1). After beingdried under vacuum for several hours, 0.81 g of4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenolwas isolated as a yellow syrup. The NMR spectrum was consistent with theproposed structure. This reaction was repeated to obtain additionalproduct for subsequent reactions.

Step C Methyl 2- 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylthiomethyl!-5-chlorophenoxy!-propionate

By the method of Example 1, Step I, 1.35 g (0.0049 mole) of4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorothiophenoland 3.0 g (0.011 mole) of methyl2-(2-chloromethyl-5-chlorophenoxy)propionate (Example 2, Step E) werereacted in the presence of 1.02 g (0.0074 mole) of anhydrous potassiumcarbonate in 75 mL of N,N-dimethylformamide, yielding 0.54 g of methyl2- 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenylthiomethyl!-5-chlorophenoxy!propionateas a yellow syrup. The NMR spectrum was consistent with the proposedstructure. NMR: 1.65 (d, 3H, J_(HH) =8.0 Hz); 2.44 (s, 3H); 3.78 (s,3H); 4.20 (dd, 2H, J_(HH) =13.0 Hz); 4.78 (q, 1H, J_(HH) =8.0 Hz);6.70-7.38 (m, 7H).

EXAMPLE 8

METHYL 2-4-(4-DIFLUOROMETHYL-4,5-DIHYDRO-3-METHYL-1,2,4-TRIAZOL-5(1H)-ON-1-YL)-3-FLUOROPHENOXYMETHYL!-5-METHYLPHENOXY!ACETATE(Compound 75)

Step A Methyl (2-formyl-5-methylphenoxy)acetate

By the method of Example 1, Step F, 8,27 g (0.060 mole) of4-methylsalicylaldehyde and 11.15 g (0.073 mole) of methyl bromoacetatewere reacted in the presence of 10.1 g (0.073 mole) of anhydrouspotassium carbonate in 150 mL of acetone, yielding 11.47 g of methyl(2-formyl-5-methylphenoxy)acetate as a white solid, m.p. 63°-64° C. TheNMR was consistent with the proposed structure.

Step B Methyl (2-hydroxymethyl-5-methylphenoxy)acetate

By the method of Example 1, Step G, 11.27 g (0.054 mole) of methyl(2-formyl-5-methylphenoxy)acetate was reacted with 0.54 g (0.014 mole)of sodium borohydride and 0.10 g (0.0018 mole) of sodium methoxide in 30of methanol, yielding 9.41 g of methyl(2-hydroxymethyl-5-methylphenoxy)acetate as a yellow oil. The NMRspectrum was consistent with the proposed structure.

Step C Methyl (2-chloromethyl-5-methylphenoxy)acetate

By the method of Example 1, Step H, 9.21 g (0.044 mole) of methyl(2-hydroxymethyl-5-methylphenoxy)acetate was reacted with 7.40 g (0.062mole) of thionyl chloride and 5 drops of pyridine in 50 mL of methylenechloride, yielding 5.57 g of methyl(2-chloromethyl-5-methylphenoxy)acetate as an orange liquid.

Step D Methyl 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!acetate

By the method of Example 1, Step I, 2.0 g (0.0077 mole) of1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one(Example 1, Step E) and 3.53 g (0.0151 mole) of methyl(2-chloromethyl-5-methylphenoxy)acetate were reacted in the presence of1.60 g (0.0116 mole) of anhydrous potassium carbonate in 40 mL ofN,N-dimethylformamide, yielding 2.75 g of methyl 2-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!-5-methylphenoxy!acetate.The NMR spectrum was consistent with the proposed structure. NMR: 2.30(s, 3H); 2.44 (s, 3H); 3.78 (s, 3H); 4.70 (s, 2H); 5.18 (s, 2H);6.60-7.36 (m, 7H).

EXAMPLE 9

2- 3-4-(4-DIFLUOROMETHYL-4,5-DIHYDRO-3-METHYL-1,2,4-TRIAZOL-5(1H)-ON-1-YL)-3-FLUOROPHENOXYMETHYL!PHENOXY!PROPIONATE(Compound 80)

Step A Methyl 2-(3-formylphenoxy)propionate

By the method of Example 1, Step F, 10.0 g (0.0819 mole) of3-hydroxybenzaldehyde and 16.0 g (0.0982 mole) of methyl2-bromopropionate were reacted in the presence of 13.6 g (0.0983 mole)of anhydrous potassium carbonate in 50 mL of N,N-dimethylformamide,yielding 16.1 g of methyl 2-(3-formylphenoxy)propionate as an orangeliquid. The NMR and IR spectra were consistent with the proposedstructure.

Step B Methyl 2-(3-hydroxymethylphenoxy)propionate

By the method of Example 1, Step G, 15.7 g (0.0761 mole) of methyl2-(3-formylphenoxy)propionate, 0.76 g (0.020 mole) of sodiumborohydride, and 0.10 g (0.0018 mole) of sodium methoxide were reactedin 40 mL of methanol, yielding 15.6 g of methyl2-(3-hydroxymethylphenoxy)propionate as a yellow liquid. The NMR and IRspectra were consistent with the proposed structure.

Step C Methyl 2-(3-chloromethylphenoxy)propionate

By the method of Example 1, Step H, 1.98 g (0.0095 mole) of methyl2-(3-hydroxymethylphenoxy)propionate and 1.24 g (0.0105 mole) of thionylchloride were reacted in the presence of five drops of pyridine in 40 mLof methylene chloride, yielding 1.93 g of methyl2-(3-chloromethylphenoxy)propionate as a yellow liquid. The NMR and IRspectra were consistent with the proposed structure.

Step D Methyl 2- 3-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!phenoxy!propionate

By the method of Example 1, Step I, 1.0 g (0.0038 mole) of1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one(Example 1, Step F) and 1.72 g (0.0076 mole) of methyl2-(3-chloromethylphenoxy)propionate were reacted in the presence of 0.79g (0.0057 mole) of anhydrous potassium carbonate in 25 mL ofN,N-dimethylformamide, yielding 1.54 g of methyl 2- 3-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!phenoxy!propionate.The NMR and IR spectra were consistent with the proposed structure. NMR:1.60 (d, 3H, J_(HH) =8.0 Hz); 2.44 (s, 3H); 3.76 (s, 3H); 4.78 (q, 1H,J_(HH) =8.0 Hz); 5.04 (s, 2H); 6.76-7.38 (m, 8H).

EXAMPLE 10

METHYL 2- 4-4-(4-DIFLUOROMETHYL-4,5-DIHYDRO-3-METHYL-1,2,4-TRIAZOL-5(1H)-ON-1-YL)-3-FLUOROPHENOXYMETHYL!PHENOXY!PROPIONATE(Compound 81)

Step A Methyl 2-(4-formylphenoxy)propionate

By the method of Example 1, Step F, 10.0 g (0.0819 mole) of4-hydroxybenzaldehyde and 16.4 g (0.0983 mole) of methyl2-bromopropionate were reacted in the presence of 13.6 g (0.0983 mole)of anhydrous potassium carbonate in N,N-dimethylformamide, yielding 12.2g of methyl 2-(4-formylphenoxy)propionate as a yellow liquid. The NMRand IR spectra were consistent with the proposed structure.

Step B Methyl 2-(4-hydroxymethylphenoxy)propionate

By the method of Example 1, Step G, 11.1 g (0.0533 mole) of methyl2-(4-formylphenoxy)propionate and 2.02 g (0.0533 mole) of sodiumborohydride were reacted in methanol, yielding 9.31 g of methyl2-(4-hydroxymethylphenoxy)propionate as a yellow oil. The NMR spectrumwas consistent with the proposed structure.

Step C Methyl 2-(4-chloromethylphenoxy)propionate

A mixture of 2.19 g (0.0104 mole) of methyl2-(4-hydroxymethylphenoxy)propionate and 3.00 g (0.0823 mole) of 36%hydrochloric acid was stirred for fifteen minutes at room temperature.The reaction mixture was then poured into ice-water, and the resultingmixture was extracted with diethyl ether. The extracts were combined andwashed in succession with water and a saturated aqueous solution ofsodium bicarbonate. The extract was dried over anhydrous magnesiumsulfate and filtered, and the solvent was evaporated from the filtrateunder reduced pressure, leaving a colorless liquid. This liquid wasplaced on a column of silica gel and eluted with methylene chloride.After the product-containing fractions were combined and the solventevaporated under reduced pressure, 1.6 g of methyl2-(4-chloromethylphenoxy)propionate was isolated as a colorless liquid.The NMR and IR spectra were consistent with the proposed structure.

Step D Methyl 2- 4-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!phenoxy!propionate

By the method of Example 1, Step I, 0.50 g (0.0019 mole) of1-(2-fluoro-4-hydroxyphenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one(Example 1, Step E) and 0.87 g (0.0038 mole) of methyl2-(4-chloromethylphenoxy)propionate were reacted in the presence of 0.2g of 1,4,7,10,13,16-hexaoxacyclooctadecane in 25 mL ofN,N-dimethylformamide, yielding 0.80 g of methyl 2- 4-4-(4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-on-1-yl)-3-fluorophenoxymethyl!phenoxy!propionateas a colorless oil that solidified upon standing, m.p. 83°-85° C. TheNMR and IR spectra were consistent with the proposed structure. NMR:1.60 (d, 3H, J_(HH) =8.0 Hz); 2.44 (s, 3H); 3.76 (s, 3H); 4.78 (q, 1H,J_(HH) =8.0 Hz); 4.90 (s, 2H); 6.78-7.38 (m, 8H).

EXAMPLE 11

METHYL 2- 2- 4-(8-THIA-1,6-DIAZABICYCLO4.3.0!NONANE-7-ON-9-YLIMINO)-3-FLUOROPHENOXYMETHYL!-5-METHYLPHENOXY!PROPIONATE(Compound 68)

Step A Methyl 2-2-(3-fluoro-4-nitrophenoxymethyl)-5-methylphenoxy!propionate

By the method of Example 1, Step I, 1.71 g (0.010 mole) of3-fluoro-4-nitrophenol and 2.85 g (0.011 mole) of methyl2-(2-chloromethyl-5-methylphenoxy)propionate were reacted in thepresence of 1.66 g (0.012 mole) of anhydrous potassium carbonate in 100mL of N,N-dimethylformamide, yielding 3.55 g of methyl 2-2-(3-fluoro-4-nitrophenoxymethyl)-5-methylphenoxy!propionate as ayellowish solid, m.p. 92°-94° C. The NMR and IR spectra were consistentwith the proposed structure.

Step B Methyl 2-2-(4-amino-3-fluorophenoxymethyl)-5-methylphenoxy!propionate

By the method of Example 2, Step A, 3.35 g (0.0091 mole) of methyl 2-2-(3-fluoro-4-nitrophenoxymethyl)-5-methylphenoxy!propionate was reactedwith 2.80 g (0.050 mole) of powdered iron in 100 mL of acetic acid,yielding 1.86 g of methyl 2-2-(4-amino-3-fluorophenoxymethyl)-5-methylphenoxy!propionate as an ambersyrup. The NMR and IR spectra were consistent with the proposedstructure.

Step C Methyl 2-2-(3-fluoro-4-isothiocyanatophenoxymethyl)-5-methylphenoxy!propionate

A solution of 1.66 g (0.005 mole) of methyl 2-2-(4-amino-3-fluorophenoxymethyl)-5-methylphenoxy!propionate and 1.26 g(0.0125 mole) of triethylamine in 40 mL of methylene chloride wasprepared at ambient temperature. To this solution was added dropwise asolution of 0.58 g (0.0050 mole) of thiophosgene in 10 mL of methylenechloride. The reaction mixture was stirred for 16 hours after which itwas filtered through a short column of silica gel. The solvent wasevaporated from the filtrate under reduced pressure, leaving 1.50 g ofmethyl 2-2-(3-fluoro-4-isothiocyanatophenoxymethyl)-5-methylphenoxy!propionate asa syrup. The NMR and IR spectra were consistent with the proposedstructure.

Step D Methyl 2- 2-4-(perhydropyridazin-1-ylthiocarbonylamino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionate

By the method of Example 1, Step C, of U.S. Pat. No. 4,906,281, 1.50 g(0.004 mole) of methyl 2-2-(3-fluoro-4-isothiocyanatophenoxymethyl)-5-methylphenoxy!propionateand 1.07 g (0.005 mole) of perhydropyridazine monohydroiodide (preparedby the method of Example 1, Step B, of U.S. Pat. No. 4,906,281) werereacted in the presence of 0.20 g (0.005 mole of sodium hydroxide in 40mL of water and 10 ML of tetrahydrofuran, yielding 1.50 g of methyl 2-2-4-(perhydropyridazin-1-ylthiocarbonylamino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionateas a syrup. The NMR spectrum was consistent with proposed structure.

Step E Methyl 2- 2- 4-(8-thia-1,6-diazabicyclo-4.3.0!nonane-7-on-9-ylimino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionate

By the method of Example 1, Step D, of U.S. Pat. No. 4,906,281, 1.50 g(0.00325 mole) of methyl 2- 2-4-(perhydropyridazin-1-ylthiocarbonylamino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionateand 0.36 g (0.09017 mole) of trichloromethyl chloroformate were reactedin the presence of 0.36 g (0.0035 mole) of triethylamine in 35 mL ofdioxane, yielding 0.50 g of methyl 2- 2- 4-(8-thia-1,6-diazabicyclo4.3.0!nonane-7-on-9-ylimino)-3-fluorophenoxymethyl!-5-methylphenoxy!propionateas a syrup. The NMR and IR spectra were consistent with the proposedstructure. NMR: 1.60 (d, 3H, J_(HH) =8.0 Hz); 1.78-1.96 (m, 4H); 2.30(s, 3H); 3.64-3.80 (m, 4H); 3.70 (s, 3H); 4.80 (q, 1H, J_(HH) =8.0 Hz);5.10 (dd, 2H); 6.58-7.30 (m, 6H).

EXAMPLE 12

METHYL 2- 24-1-METHYL-7-TRIFLUOROMETHYL-2,4-(1H,3H)PYRIMIDINEDION-3-YL)PHENOXYMETHYL!-5-METHYLPHENOXY!PROPIONATE(Compound 87)

Step A1-Methyl-3-(4-methoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

In a flask was placed 8.27 g (0.207 mole) of a 60% suspension of sodiumhydride in mineral oil. The mineral oil was removed by washing thesodium hydride twice with heptane. To the flask was then added 300 mL oftetrahydrofuran. This suspension was cooled to -20° C. at which it wasmaintained during the dropwise addition of 37.9 g (0.207 mole) of3-amino-4,4,4-trifluorocrotonate. This mixture was allowed to stir for10 minutes before the dropwise addition of 30.83 g (0.207 mole) of4-methoxyphenyl isocyanate was commenced. Upon completion of addition,the reaction mixture was heated at reflux for approximately 16 hours. Atthe conclusion of this period the reaction mixture was cooled to ambienttemperature, and 28.56 g (0.207 mole) of potassium carbonate and 58.75 g(0.228 mole) of methyl iodide were added to it. The reaction mixture wasthen heated at reflux for seven hours. At the conclusion of this periodthe reaction mixture was cooled, and diethyl ether and water were addedto it. The aqueous phase was separated from the organic phase. Thelatter was washed with water, dried over anhydrous magnesium sulfate,and filtered. The filtrate was concentrated under reduced pressure,leaving a residue. This residue was passed through a column of silicagel, eluting with ethyl acetate/heptane mixtures starting with 1:8 andconcluding with 1:1. The product-containing fractions were combined, andthe solvent was evaporated under reduced pressure, yielding 27.1 g of1-methyl-3-(4-methoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione.The NMR spectrum was consistent with the proposed structure.

Step B1-Methyl-3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione

In a flask were placed 25.88 g (0.086 mole) of1-methyl-3-(4-methoxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedioneand 200 mL of methylene chloride. To this flask was added dropwise 258mL (0.258 mole) of a 1 molar solution of boron tribromide in methylenechloride. Upon completion of addition, this reaction mixture was allowedto stir at ambient temperature for approximately 64 hours after which itwas poured over ice. This mixture was filtered to remove insolublematerial, and the aqueous and organic layers of the filtrate wereseparated. The organic layer was washed with water, dried over anhydrousmagnesium sulfate, and filtered. The filtrate was evaporated underreduced pressure, leaving1-methyl-3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedioneas a residue. The NMR spectrum was consistent with proposed structure.

Step C Methyl 2- 2-4-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedion-3-yl)phenoxymethyl!-5-methylphenoxy!propionate

By the method of Example 1, Step I, 0.7 g (0.0029 mole) of methyl2-(2-chloromethyl-5-methylphenoxy)propionate (Example 1, Step H), 0.30 g(0.0011 mole) of1-methyl-3-(4-hydroxyphenyl)-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedione,and 0.22 g (0.0016 mole) of potassium carbonate were reacted in 80 mL ofN,N-dimethylformamide, yielding 0.33 g of methyl 2- 2-4-(1-methyl-6-trifluoromethyl-2,4(1H,3H)-pyrimidinedion-3-yl)phenoxymethyl!-5-methylphenoxy!propionate(Compound 87) as a yellow solid, m.p. 52°-54° C. The NMR spectrum wasconsistent with the proposed structure.

Representative compounds of the invention prepared by the methodsexemplified above are shown in Table 1. Characterizing data are given inTable 2.

HERBICIDAL ACTIVITY

The 2-(4-heterocyclic-substituted-3-halophenoxymethyl)phenoxy!alkanoates ofthis invention were tested in pre- and postemergence evaluations using avariety of broadleaf and grasseous crops and weeds. The test speciesused to demonstrate the herbicidal activity of these compounds includesoybean (Glycine max var. Williams), field corn (Zea mays var. Agway425X), wheat (Triticum aestivum var. Wheaton), morningglory (Ipomealacunosa or Ipomea hederacea), velvetleaf (Abutilon theophrasti), greenfoxtail (Setaria viridis), Johnsongrass (Sorghum halepense), blackgrass(Alopecurus myosuroides), common chickweed (Stellaria media), and commoncocklebur (Xanthium pensylvanicum).

Preparation of Flats

For preemergence testing two disposable fiber flats (8 cm×15 cm×25 cm)for each rate of application of each candidate herbicide were filled toan approximate depth of 6.5 cm with steam-sterilized sandy loam soil.The soil was leveled and impressed with a template to provide fiveevenly spaced furrows 13 cm long and 0.5 cm deep in each flat. Seeds ofsoybean, wheat, corn, green foxtail, and Johnsongrass were planted inthe furrows of the first flat, and seeds of velvetleaf, morningglory,common chickweed, cocklebur, and blackgrass were planted in the furrowsof the second flat. The five-row template was employed to firmly pressthe seeds into place. A topping soil of equal portions of sand and sandyloam soil was placed uniformly on top of each flat to a depth ofapproximately 0.5 cm. Flats for postemergence testing were prepared inthe same manner, except that they were planted 8-12 days prior to thepreemergence flats and were placed in a greenhouse and watered, thusallowing the seeds to germinate and the foliage to develop.

A stock solution of the candidate herbicide was prepared by dissolving apredetermined weight of the compound in 20 ml of water/acetone (50/50)containing 0.5% v/v sorbitan monolaurate. Thus for an application rateof 3000 g/ha of herbicide, 0.21 g of candidate herbicide was dissolvedin 20 ml of the aqueous acetone to prepare the stock solution. For the300 g/ha rate of application used in most of the tests reported below, a1.0 mL portion of stock solution was diluted with water/acetone (50/50)to 35 ml, the volume required for a spray volume of 1000 L/ha. Theremaining stock solution was then used to prepare spray solutions forother application rates.

The spray solution (35 ml) was then sprayed on the four flatssimultaneously, i.e., to the surface of the soil of the preemergenceflats and to the emerged foliage of the postemergence flats. All flatswere placed in the greenhouse, but only the preemergence flats werewatered immediately. The foliage of the postemergence flats was kept dryfor 24 hours, after which regular watering commenced. Phytotoxicitydata, taken as percent control, were recorded 17-21 days after thechemical was applied.

Percent control was determined by a method similar to the 0 to 100rating system disclosed in "Research Methods in Weed Science," 2nd ed.,B. Truelove, Ed.; Southern Weed Science Society; Auburn University,Auburn, Ala., 1977. The rating system is as follows:

    ______________________________________                                        Herbicide Rating System                                                       Rating  Description                                                           Percent of Main    Crop         Weed                                          Control Categories Description  Description                                   ______________________________________                                         0      No effect  No crop      No weed                                                          reduction    control                                                          or injury                                                  10                 Slight dis-  Very poor weed                                                   coloration   control                                                          or stunting                                                20      Slight     Some dis-    Poor weed                                             effect     coloration,  control                                                          stunting or                                                                   stand loss                                                 30                 Crop injury  Poor to defi-                                                    more pronounced                                                                            cient weed                                                       but not lasting                                                                            control                                       40                 Moderate injury,                                                                           Deficient weed                                                   crop usually control                                                          recovers                                                   50      Moderate   Crop injury  Deficient to                                          effect     more lasting,                                                                              moderate weed                                                    recovery doubtful                                                                          control                                       60                 Lasting crop Moderate weed                                                    injury, no   control                                                          recovery                                                   70                 Heavy injury and                                                                           Control some-                                                    stand loss   what less than                                                                satisfactory                                  80      Severe     Crop nearly des-                                                                           Satisfactory                                                     troyed, a few                                                                              to good weed                                                     survivors    control                                       90                 only occasional                                                                            Very good to                                                     live plants left                                                                           excellent                                     control                                                                       100     Complete   Complete crop                                                                              Complete weed                                         effect     destruction  destruction                                   ______________________________________                                    

Herbicidal data at 300 or 250 g/ha are presented in Table 2(preemergence activity) and Table 4 (postemergence activity). The testcompounds are identified in Tables 2 and 3 by numbers which correspondto those in Table 1.

For herbicidal application the active compounds are formulated intoherbicidal compositions by admixture in herbicidally effective amountswith adjuvants and carriers normally employed in the art forfacilitating the dispersion of active ingredients for the particularutility desired, recognizing the fact that the formulation and mode ofapplication of a toxicant may affect the activity of the material in agiven application. Thus, for agricultural use the present herbicidalcompounds may be formulated as granules of relatively large particlesize, as water-soluble or water-dispersible granules, as powdery dusts,as wettable powders, as emulsifiable concentrates, as solutions, or asany of several other known types of formulations, depending on thedesired mode of application.

These herbicidal compositions may be applied either as water-dilutedsprays, or dusts, or granules to the areas in which suppression ofvegetation is desired. These formulations may contain as little as 0.1%,0.2% or 0.5% to as much as 95% or more by weight of active ingredient.

Dusts are free flowing admixtures of the active ingredient with finelydivided solids such as talc, natural clays, kieselguhr, flours such aswalnut shell and cottonseed flours, and other organic and inorganicsolids which act as dispersants and carriers for the toxicant; thesefinely divided solids have an average particle size of less than about50 microns. A typical dust formulation useful herein is one containing1.0 part or less of the herbicidal compound and 99.0 parts of talc.

Wettable powders, also useful formulations for both pre- andpostemergence herbicides, are in the form of finely divided particleswhich disperse readily in water or other dispersant. The wettable powderis ultimately applied to the soil either as a dry dust or as an emulsionin water or other liquid. Typical carriers for wettable powders includeFuller's earth, kaolin clays, silicas, and other highly absorbent,readily wet inorganic diluents. Wettable powders normally are preparedto contain about 5-80% of active ingredient, depending on the absorbencyof the carrier, and usually also contain a small amount of a wetting,dispersing or emulsifying agent to facilitate dispersion. For example, auseful wettable powder formulation contains 80.8 parts of the herbicidalcompound, 17.9 parts of Palmetto clay, and 1.0 part of sodiumlignosulfonate and 0.3 part of sulfonated aliphatic polyester as wettingagents. Frequently additional wetting agent and/or oil will be added tothe tank mix for postemergence application to facilitate dispersion onthe foliage and absorption by the plant.

Other useful formulations for herbicidal applications are emulsifiableconcentrates (ECs) which are homogeneous liquid compositions dispersiblein water or other dispersant, and may consist entirely of the herbicidalcompound and a liquid or solid emulsifying agent, or may also contain aliquid carrier, such as xylene, heavy aromatic naphthas, isophorone, orother non-volatile organic solvent. For herbicidal application theseconcentrates are dispersed in water or other liquid carrier, andnormally applied as a spray to the area to be treated. The percentage byweight of the essential active ingredient may vary according to themanner in which the composition is to be applied, but in generalcomprises 0.5 to 95% of active ingredient by weight of the herbicidalcomposition.

Flowable formulations are similar to ECs except that the activeingredient is suspended in a liquid carrier, generally water. Flowables,like ECs, may include a small amount of a surfactant, and contain activeingredient in the range of 0.5 to 95%, frequently from 10 to 50%, byweight of the composition. For application, flowables may be diluted inwater or other liquid vehicle, and are normally applied as a spray tothe area to be treated.

Typical wetting, dispersing, or emulsifying agents used in agriculturalformulations include, but are not limited to, the alkyl and alkylarylsulfonates and sulfates and their sodium salts; alkylaryl polyetheralcohols; sulfated higher alcohols; polyethylene oxides; sulfonatedanimal and vegetable oils; sulfonated petroleum oils; fatty acid estersof polyhydric alcohols and the ethylene oxide addition products of suchesters; and the addition product of long-chain mercaptans and ethyleneoxide. Many other types of useful surface-active agents are available incommerce. The surface-active agent, when used, normally comprises from 1to 15% by weight of the composition.

Other useful formulations include suspensions of the active ingredientin a relatively non-volatile liquid such as water, corn oil, kerosene,propylene glycol, or other suitable liquid carrier.

Still other useful formulations for herbicidal applications includesimple solutions of the active ingredient in a solvent in which it iscompletely soluble at the desired concentration, such as acetone,alkylated naphthalenes, xylene, or other organic solvents. Granularformulations, wherein the toxicant is carried on relatively coarseparticles, are of particular utility for aerial distribution or forpenetration of cover crop canopy. Pressurized sprays, typically aerosolswherein the active ingredient is dispersed in finely divided form as aresult of vaporization of a low boiling dispersant solvent carrier, suchas the Freon fluorinated hydrocarbons, may also be used. Water-solubleor water-dispersible granules are also useful formulations forherbicidal application of the present compounds. Such granularformulations are free-flowing, non-dusty, and readily water-soluble orwater-miscible. The soluble or dispersible granular formulationsdescribed in U.S. Pat. No. 3,920,442 are useful with the presentherbicidal compounds. In use by the farmer on the field, the granularformulations, emulsifiable concentrates, flowable concentrates,solutions, etc., may be diluted with water to give a concentration ofactive ingredient in the range of say 0.1% or 0.2% to 1.5% or 2%.

The active herbicidal compounds of this invention may be formulatedand/or applied with insecticides, fungicides, nematicides, plant growthregulators, fertilizers, or other agricultural chemicals and may be usedas effective soil sterilants as well as selective herbicides inagriculture. In applying an active compound of this invention, whetherformulated alone or with other agricultural chemicals, an effectiveamount and concentration of the active compound is of course employed;the amount may be as low as, e.g. about 10 to 100 g/ha, preferably about30 to 60 g/ha. For field use, where there are losses of herbicide,higher application rates (e.g., four times the greenhouse testing ratesmentioned above) may be employed.

The active herbicidal compounds of this invention may be used incombination with other herbicides, e.g., they may be mixed with, say, alesser, equal, or larger amount of a known herbicide such asaryloxyalkanoic acid herbicides such as (2,4-dichlorophenoxy)acetic acid(2,4-D), (4-chloro-2-methylphenoxy)acetic acid (MCPA),(±)-2-(4-chloro-2-methylphenoxy)propanoic acid (MCPP); urea herbicides,such as N,N-dimethyl-N'- 4-(1-methylethyl)phenyl!urea (isoproturon);imidazolinone herbicides, such as 2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-3-pyridinecarboxylicacid (imazapyr), a reaction product comprising (±)-2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-4-methylbenzoicacid and (±)-2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-5-methylbenzoicacid (imazamethabenz), (±)-2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-5-ethyl-3-pyridinecarboxylicacid (imazethapyr), and (±)-2-4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl!-3-quinolinecarboxylicacid (imazaquin); diphenyl ether herbicides, such as 5-2-chloro-4-(trifluoromethyl)phenoxy!-2-nitrobenzoic acid (acifluorfen),methyl 5-(2,4-dichlorophenoxy)-2-nitrobenzoate (bifenox), and 5-2-chloro-4-(trifluoromethyl)phenoxy!-N-(methylsulfonyl)-2-nitrobenzamide(fomasafen); hydroxybenzonitrile herbicides, such as4-hydroxy-3,5-diiodobenzonitrile (ioxynil), and3,5-dibromo-4-hydroxybenzonitrile (bromoxynil); sulfonylurea herbicides,such as 2-(4-chloro-6-methoxy-2-pyrimidinyl)amino!carbonyl!amino!sulfonyl!benzoicacid (chlorimuron), 2-chloro-N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino!carbonyl!benzenesulfonamide(chlorsulfuron), 2-(4,6-dimethoxy-2-pyrimidinyl)amino!carbonyl!amino!sulfonyl!methyl!benzoicacid (bensulfuron), 2-(4,6-dimethoxy-2-pyrimidinyl)amino!carbonyl!amino!sulfonyl!-1-methyl-1H-pyrazol-4-carboxylicacid (pyrazosulfuron), 3-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino!carbonyl!amino!sulfonyl!-2-thiophenecarboxylicacid (thifensulfuron), and 2-(2-chloroethoxy)-N-(4-methoxy-6-methyl-1,3,5-triazin-2-yl)amino!carbonyl!benzenesulfonamide(triasulfuron); 2-(4-aryloxyphenoxy)alkanoic acid herbicides, such as(±)-2- 4- (6-chloro-2-benzoxazolyl)oxy!phenoxy!propanoic acid(fenoxaprop), (±)-2- 4-5-(trifluoromethyl)-2-pyridinyl!oxy!phenoxy!propanoic acid (fluazifop),(±)-2- 4-(6-chloro-2-quinoxalinyl)oxy!phenoxy!propanoic acid(quizalofop), and (±)-2- -(2,4-dichlorophenoxy)phenoxy!propanoic acid(diclofop); benzothiadiazinone herbicides, such as3-(1-methylethyl)-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide(bentazone); 2-chloroacetanilide herbicides, such asN-(butoxymethyl)-2-chloro-2',6'-diethylacetanilide (butachlor);arenecarboxylic acid herbicides, such as 3,6-dichloro-2-methoxybenzoicacid (dicamba); and pyridyloxyacetic acid herbicides, such as(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy!acetic acid (fluroxypyr).

One use of the active herbicides of this invention is in combinationwith grass-controlling herbicides, such as glyphosate, sephoxydim,quizalofop, or fluazifop. For example, the postemergence application ofcombinations of Compound 90 of this invention, 2- 2-4-(1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione-3-yl)phenoxymethyl!-5-ethylphenoxy!propionate,with glyphosate have given better control of several weed species,including velvetleaf, morningglory, yellow nutsedge, and barnyardgrass,than either component alone. Such combinations may advantageouslyapplied for control of undesired plants in corn, soybeans, cereals,vineyards and orchards.

The active herbicides of this invention may also be used in combinationwith other herbicide such as 2,4-D or clethodim for enhanced control ofbroadleaves.

It is apparent that various modifications may be made in the formulationand application of the compounds of this invention without departingfrom the inventive concepts herein as defined in the claims.

                                      TABLE 1                                     __________________________________________________________________________    Compound                                                                      No.   Q.sup.a                                                                          X    Y   Z     Z'  R                                                 __________________________________________________________________________     ##STR17##                                                                    1     A  H    H   H     H   CH.sub.3                                          2     A  F    H   H     H   H                                                 3     A  F    H   H     H   CH.sub.3                                          4     A  F    H   4-F   H   CH.sub.3                                          5     A  F    H   3-Cl  H   CH.sub.3                                          6     A  F    H   4-Cl  H   H                                                 7     A  F    H   4-Cl  H   CH.sub.3                                          8     A  F    H   5-Cl  H   CH.sub.3                                          9     A  F    H   4-Br  H   CH.sub.3                                          10    A  F    H   3-F   4-F CH.sub.3                                          11    A  F    H   3-Cl  4-Cl                                                                              CH.sub.3                                          12    A  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          13    A  F    H   5-OCH.sub.3                                                                         H   CH.sub.3                                          14    A  Cl   H   H     H   CH.sub.3                                          15    A  Cl   H   H     H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      16    A  Cl   H   4-F   H   CH.sub.3                                          17    A  Cl   H   3-Cl  H   CH.sub.3                                          18    A  Cl   H   4-Cl  H   CH.sub.3                                          19    A  Cl   H   4-Br  H   CH.sub.3                                          20    A  Cl   H   3-F   4-F CH.sub.3                                          21    A  Cl   H   3-Cl  4-Cl                                                                              CH.sub.3                                          22    A  Cl   H   4-CH.sub.3                                                                          H   CH.sub.3                                          23    B  H    H   H     H   CH.sub.3                                          24    B  F    H   H     H   CH.sub.3                                          25    B  F    H   4-F   H   CH.sub.3                                          26    B  F    H   3-Cl  H   CH.sub.3                                          27    B  F    H   4-Cl  H   CH.sub.3                                          28    B  F    H   5-Cl  H   CH.sub.3                                          29    B  F    H   4-Br  H   CH.sub.3                                          30    B  F    H   3-F   4-F CH.sub.3                                          31    B  F    H   3-Cl  4-Cl                                                                              CH.sub.3                                          32    B  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          33    B  Cl   H   4-F   H   CH.sub.3                                          34    B  Cl   H   3-Cl  H   CH.sub.3                                          35    B  Cl   H   4-Cl  H   CH.sub.3                                          36    B  Cl   H   4-Br  H   CH.sub.3                                          37    B  Cl   H   3-Cl  4-Cl                                                                              CH.sub.3                                          38    B  Cl   H   4-CH.sub.3                                                                          H   CH.sub.3                                          39    B  3-OC(CH.sub.3).sub.2 CH.sub.2 -2                                                       H     H   CH.sub.3                                          40    B  3-OC(CH.sub.3).sub.2 CH.sub.2 -2                                                       4-Cl  H   CH.sub.3                                          41    C  F    H   H     H   CH.sub.3                                          42    C  F    H   4-F   H   CH.sub.3                                          43    C  F    H   3-Cl  H   CH.sub.3                                          44    C  F    H   4-Cl  H   CH.sub.3                                          45    C  F    H   3-Cl  4-Cl                                                                              CH.sub.3                                          46    A  F    H   4-Cl  6-Cl                                                                              CH.sub.3                                          47    A  F    H   4-CH.sub.3                                                                          H   H                                                 48    A  F    H   4-CH.sub.3                                                                          H   C.sub.2 H.sub.5                                   49    A  F    H   4-CH.sub.3                                                                          H   i-C.sub.3 H.sub.7                                 50    A  F    H   4-C.sub.2 H.sub.5                                                                   H   H                                                 51    A  F    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          52    A  F    H   4-C.sub.3 H.sub.7                                                                   H   CH.sub.3                                          53    A  F    H   4-i-C.sub.3 H.sub.7                                                                 H   CH.sub.3                                          54    A  F    H   4-C.sub.4 H.sub.9                                                                   H   CH.sub.3                                          55    A  F    H   4-t-C.sub.4 H.sub.9                                                                 H   CH.sub.3                                          56    A  F    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3 OCH.sub.2 CH(CH.sub.3)                   57    A  F    H   4-CH.sub.3                                                                          H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      58    A  F    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      59    A  F    H   4-t-C.sub.4 H.sub.9                                                                 H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      60    A  F    H   4-φ                                                                             H   CH.sub.3                                          61    A  F    H   3-(CH.sub.2).sub.4 -4                                                                   CH.sub.3                                          62    A  Cl   H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          63    D  F    H   4-Cl  H   CH.sub.3                                          64    D  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          65    D  F    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          66    E  F    H   4-Cl  H   CH.sub.3                                          67    E  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          68    F  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          69    G  F    H   4-Cl  H   CH.sub.3                                          70    G  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          71    G  F    H   4-C.sub.3 H.sub.7                                                                   H   CH.sub.3                                          R' = CH.sub.3, W = S                                                          72    A  F    H   4-Cl  H   CH.sub.3                                          73    A  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          R' = H, W = O                                                                 74    A  F    H   H     H   CH.sub.3                                          75    A  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          76    A  F    H   4-CH.sub.3                                                                          H   H                                                 77    B  F    H   H     H   CH.sub.3                                          78    D  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                           ##STR18##                                                                    79    A  F    H   H     H   H                                                 80    A  F    H   H     H   CH.sub.3                                           ##STR19##                                                                    81    A  F    H   H     H   CH.sub.3                                          82    A  F    H   H     H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      83    A  Cl   H   H     H   CH.sub.3                                          84    B  F    H   H     H   CH.sub.3                                           ##STR20##                                                                    85    H  H    H   H     H   CH.sub.3                                          86    H  H    H   4-Cl  H   CH.sub.3                                          87    H  H    H   4-CH.sub.3                                                                          H   CH.sub.3                                          88    H  H    H   4-CH.sub.3                                                                          H   i-C.sub.3 H.sub.7                                 89    H  H    H   4-CH.sub.3                                                                          H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      90    H  H    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          91    H  H    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3 O(CH.sub.2).sub.2 O(CH.sub.2).sub.2      92    H  H    H   4-C.sub.3 H.sub.7                                                                   H   CH.sub.3                                          93    H  H    H   4-CH.sub.3 O                                                                        H   CH.sub.3                                          94    H  F    H   4-Cl  H   CH.sub.3                                          95    H  F    H   4-CH.sub.3                                                                          H   CH.sub.3                                          96    H  F    H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          97    H  F    H   4-C.sub.3 H.sub.7                                                                   H   CH.sub.3                                          98    H  Cl   H   4-Cl  H   CH.sub.3                                          99    H  Cl   H   4-CH.sub.3                                                                          H   CH.sub.3                                          100   H  CH.sub.3                                                                           H   4-Cl  H   CH.sub.3                                          101   H  CH.sub.3                                                                           H   4-CH.sub.3                                                                          H   CH.sub.3                                          102   H  CH.sub.3                                                                           H   4-C.sub.2 H.sub.5                                                                   H   CH.sub.3                                          103   H  H    H   4-CH.sub.3                                                                          H   CCl.sub.3 CH.sub.2                                104   H  H    H   4-C.sub.2 H.sub.5                                                                   H   CCl.sub.3 CH.sub.2                                __________________________________________________________________________     .sup.a. -                                                                     ##STR21##                                                                     ##STR22##                                                                     ##STR23##                                                                     ##STR24##                                                                     ##STR25##                                                                     ##STR26##                                                                     ##STR27##                                                                     ##STR28##                                                                

                  TABLE 2                                                         ______________________________________                                        Characterizing Data                                                           Com-           Com-            Com-                                           pound MP       pound   HP      pound MP                                       No.   °C.                                                                             No.     °C.                                                                            No.   °C.                               ______________________________________                                        1     oil      35      109-111 69    glass                                    2     74-76    36      oil     70    stiff syrup                              3     oil      37      oil     71    stiff syrup                              4     84-87    38      oil     72    syrup                                    5     oil      39      oil     73    syrup                                    6     oil      40      oil     74    94-97                                    7     oil      41      oil     75    thick yellow liq.                        8     86-88    42      oil     76    110-112                                  9     86-88    43      oil     77    123-125                                  10    103-105  44      oil     78    syrup                                    11    94-96    45      oil     79    oil                                      12    74-76    46      oil     80    oil                                      13    oil      47      gel     81    83-85                                    14    oil      48       98-101 82    oil                                      15    oil      49      oil     83    oil                                      16    89-92    50      yellow liq.                                                                           84      118-119.5                              17    oil      51      yellow liq.                                                                           85    oil                                      18    87-89    52      yellow syrup                                                                          86    oil                                      19    89-92    53      oil     87    52-54                                    20    80-82    54      syrup   88    oil                                      21    68-70    55      orange oil                                                                            89    oil                                      22    oil      56      yellow oil                                                                            90    oil                                      23    131-133  57      gel     91    oil                                      24    oil      58      yellow oil                                                                            92    75-78                                    25    83-86    59      yellow oil                                                                            93    oil                                      26    141-143  60      orange oil                                                                            94    oil                                      27    110-112  61      syrup   95    oil                                      28    102-103  62      yellow liq.                                                                           96    oil                                      29    113-115  63      syrup   97    oil                                      30    73-76    64      oil     98    oil                                      31    oil      65      syrup   99    oil                                      32    81-83    66      syrup   100   oil                                      33    oil      67      syrup   101   oil                                      34    116-118  68      syrup   102   oil                                      ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                        PREEMERGENCE HERBICIDAL ACTIVITY (% Control)                                  ______________________________________                                        Compound No. 1      2          3    4                                         Rate (kg/ha) 0.3    0.3        0.25 0.3                                       ______________________________________                                        Species                                                                       Soybean      0      0          90   80                                        Wheat        70     80         20   80                                        Corn         15     15         15   70                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    90     80         90   100                                       Cocklebur    10     20         70   80                                        Blackgrass   80     40         70   95                                        Green foxtail                                                                              90     80         100  100                                       Johnsongrass 80     70         70   95                                        ______________________________________                                        Compound No. 5      6          7    8                                         Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      10     10         50   0                                         Wheat        10     50         95   0                                         Corn         20     85         10   5                                         Velvetleaf   100    100        100  85                                        Morningglory 100    100        100  85                                        Chickweed    100    100        100  90                                        Cocklebur    70     100        100  0                                         Blackgrass   90     100        100  0                                         Green foxtail                                                                              100    100        100  10                                        Johnsongrass 95     80         70   40                                        ______________________________________                                        Compound No. 9      10         11   12                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    10         0    20                                        Wheat        80     20         10   70                                        Corn         95     10         10   50                                        Velvetleaf   100    100        100  100                                       Morningglory 100    95         100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    40         60   90                                        Blackgrass   100    70         20   80                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 95     40         90   60                                        ______________________________________                                        Compound No. 13     14*        15   16                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      0          0    10                                        Wheat        0      5          5    10                                        Corn         5      10         5    15                                        Velvetleaf   100    85         100  100                                       Morningglory 60     70         100  100                                       Chickweed    20     45         90   100                                       Cocklebur    30     0          5    60                                        Blackgrass   0      0          0    20                                        Green foxtail                                                                              85     75         50   100                                       Johnsongrass 10     30         0    60                                        ______________________________________                                        Compound No. 17     18         19   20                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      10     0          60   0                                         Wheat        70     10         --   0                                         Corn         10     30         20   0                                         Velvetleaf   100    100        100  100                                       Morningglory 30     90         90   80                                        Chickweed    40     100        100  50                                        Cocklebur    20     40         60   0                                         Blackgrass   80     10         90   10                                        Green foxtail                                                                              90     100        100  100                                       Johnsongrass 95     90         90   60                                        ______________________________________                                        Compound No. 21     22         23   24                                        Rate (kg/ha) 0.3    0.3        0.3  0.25                                      ______________________________________                                        Species                                                                       Soybean      0      10         --   5                                         Wheat        0      60         5    10                                        Corn         30     50         5    5                                         Velvetleaf   100    100        30   80                                        Morningglory 70     90         100  70                                        Chickweed    20     80         85   95                                        Cocklebur    20     10         0    20                                        Blackgrass   10     30         5    90                                        Green foxtail                                                                              95     95         40   30                                        Johnsongrass 70     50         60   15                                        ______________________________________                                        Compound No. 25     26         27   28                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      20     0          10   90                                        Wheat        20     0          0    95                                        Corn         10     0          15   95                                        Velvetleaf   100    85         100  50                                        Morningglory 100    95         100  20                                        Chickweed    100    --         100  85                                        Cocklebur    80     10         80   0                                         Blackgrass   0      40         70   60                                        Green foxtail                                                                              60     20         0    15                                        Johnsongrass 10     0          40   85                                        ______________________________________                                        Compound No. 29     30         31   32                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      90     40         10   30                                        Wheat        0      0          0    0                                         Corn         20     0          0    0                                         Velvetleaf   100    100        100  100                                       Morningglory 100    90         95   100                                       Chickweed    100    95         10   100                                       Cocklebur    85     100        20   80                                        Blackgrass   --     30         10   30                                        Green foxtail                                                                              95     70         0    100                                       Johnsongrass 80     10         10   10                                        ______________________________________                                        Compound No. 33     34         35   36                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      0          0    0                                         Wheat        0      0          0    0                                         Corn         15     0          10   0                                         Velvetleaf   100    95         100  100                                       Morningglory 100    90         95   80                                        Chickweed    100    --         95   100                                       Cocklebur    10     10         10   20                                        Blackgrass   0      10         10   10                                        Green foxtail                                                                              70     0          0    10                                        Johnsongrass 10     0          20   0                                         ______________________________________                                        Compound No. 37     38         39   40                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      0          10   10                                        Wheat        0      0          --   10                                        Corn         0      0          --   0                                         Velvetleaf   80     70         0    0                                         Morningglory 60     20         10   0                                         Chickweed    0      50         --   100                                       Cocklebur    0      10         0    10                                        Blackgrass   0      0          0    0                                         Green foxtail                                                                              10     40         --   0                                         Johnsongrass 10     10         20   10                                        ______________________________________                                        Compound No. 41     42         43   44                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      0          0    20                                        Wheat        0      0          0    0                                         Corn         0      50         30   20                                        Velvetleaf   --     0          0    80                                        Morningglory 10     0          0    80                                        Chickweed    0      0          0    80                                        Cocklebur    10     20         0    70                                        Blackgrass   0      0          0    10                                        Green foxtail                                                                              10     0          0    20                                        Johnsongrass 30     0          20   30                                        ______________________________________                                        Compound No. 45     46         47   48                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      20         30   90                                        Wheat        0      10         75   90                                        Corn         0      10         75   90                                        Velvetleaf   0      100        100  100                                       Morningglory --     95         100  100                                       Chickweed    0      100        100  100                                       Cocklebur    --     60         75   100                                       Blackgrass   0      40         95   95                                        Green foxtail                                                                              0      100        100  100                                       Johnsongrass 0      90         75   90                                        ______________________________________                                        Compound No. 49     50         51   52                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      75     60         80   90                                        Wheat        85     75         80   20                                        Corn         75     30         75   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    85         100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    75         85   95                                        Blackgrass   90     80         80   40                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    80         95   90                                        ______________________________________                                        Compound No. 53     54         55   56                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    95         70   90                                        Wheat        80     0          20   50                                        Corn         40     30         30   40                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    90     50         80   75                                        Blackgrass   100    20         75   75                                        Green foxtail                                                                              100    95         95   100                                       Johnsongrass 70     70         75   95                                        ______________________________________                                        Compound No. 57     58         59   60                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      40     60         50   75                                        Wheat        80     75         20   20                                        Corn         75     40         20   20                                        Velvetleaf   100    100        100  100                                       Morningglory 95     100        85   100                                       Chickweed    100    100        90   100                                       Cocklebur    70     30         75   60                                        Blackgrass   80     75         70   60                                        Green foxtail                                                                              100    100        90   100                                       Johnsongrass 80     90         80   70                                        ______________________________________                                        Compound No. 61     62         63   64                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      40     40         40   30                                        Wheat        20     70         10   20                                        Corn         20     50         10   30                                        Velvetleaf   100    100        100  100                                       Morningglory 80     100        100  90                                        Chickweed    70     100        100  100                                       Cocklebur    10     60         75   60                                        Blackgrass   40     85         70   30                                        Green foxtail                                                                              100    100        100  50                                        Johnsongrass 70     80         75   30                                        ______________________________________                                        Compound No. 65     66         67   68                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      85     10         10   40                                        Wheat        10     10         10   10                                        Corn         10     0          10   10                                        Velvetleaf   100    80         100  100                                       Morningglory 100    10         100  90                                        Chickweed    100    0          60   100                                       Cocklebur    80     10         30   40                                        Blackgrass   50     30         60   30                                        Green foxtail                                                                              100    0          75   80                                        Johnsongrass 80     0          10   40                                        ______________________________________                                        Compound No. 69     70         71   72                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      60     20         85   40                                        Wheat        40     40         20   40                                        Corn         20     50         30   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  95                                        Chickweed    100    100        100  100                                       Cocklebur    90     30         85   75                                        Blackgrass   40     0          0    75                                        Green foxtail                                                                              100    100        100  90                                        Johnsongrass 95     20         75   50                                        ______________________________________                                        Compound No. 73     74         75   76                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      0      10         10   20                                        Wheat        0      80         60   60                                        Corn         0      20         20   70                                        Velvetleaf   100    100        100  100                                       Morningglory 80     100        100  100                                       Chickweed    100    80         75   80                                        Cocklebur    20     0          10   30                                        Blackgrass   70     95         75   60                                        Green foxtail                                                                              100    80         100  100                                       Johnsongrass 30     70         70   80                                        ______________________________________                                        Compound No. 77     78         79   80                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      10     10         0    0                                         Wheat        5      20         10   85                                        Corn         10     10         20   5                                         Velvetleaf   10     100        100  100                                       Morningglory 80     100        95   100                                       Chickweed    20     30         95   90                                        Cocklebur    10     60         0    20                                        Blackgrass   5      30         40   50                                        Green foxtail                                                                              20     80         70   100                                       Johnsongrass 20     50         95   80                                        ______________________________________                                        Compound,No. 81     82         83   84                                        Rate (kg/ha) 0.25   0.25       0.3  0.25                                      ______________________________________                                        Species                                                                       Soybean      0      0          0    10                                        Wheat        0      5          5    0                                         Corn         10     40         5    5                                         Velvetleaf   50     95         0    0                                         Morningglory 80     85         0    10                                        Chickweed    15     30         90   5                                         Cocklebur    20     40         0    5                                         Blackgrass   60     60         0    0                                         Green foxtail                                                                              95     85         --   30                                        Johnsongrass 10     80         5    10                                        ______________________________________                                        Compound No. 85     86         87   88                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      60     85         75   90                                        Wheat        10     30         50   0                                         Corn         75     75         60   20                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    45     100        70   50                                        Blackgrass   90     75         60   20                                        Green foxtail                                                                              100    90         95   100                                       Johnsongrass 90     95         95   30                                        ______________________________________                                        Compound No. 89     90         91   92                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    100        100  95                                        Wheat        30     90         10   0                                         Corn         75     90         90   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    95         90   95                                        Blackgrass   95     60         85   40                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        100  95                                        ______________________________________                                        Compound No. 93     94         95   96                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      40     100        90   95                                        Wheat        20     0          10   60                                        Corn         40     45         85   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        95   100                                       Chickweed    100    100        100  100                                       Cocklebur    75     100        100  90                                        Blackgrass   75     85         70   40                                        Green foxtail                                                                              70     100        100  100                                       Johnsongrass 75     100        95   75                                        ______________________________________                                        Compound No. 97     98         99   100                                       Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      95     10         20   50                                        Wheat        20     0          0    0                                         Corn         30     20         20   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    60         20   90                                        Chickweed    100    100        ND   100                                       Cocklebur    90     40         40   80                                        Blackgrass   30     0          20   20                                        Green foxtail                                                                              95     70         100  100                                       Johnsongrass 60     40         80   80                                        ______________________________________                                        Compound No. 101    102        103  104                                       Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      70     75         60   100                                       Wheat        10     0          60   20                                        Corn         75     10         80   60                                        Velvetleaf   100    100        100  100                                       Morningglory 60     60         100  100                                       chickweed    100    95         100  100                                       Cocklebur    60     70         90   80                                        Blackgrass   30     0          95   80                                        Green foxtail                                                                              95     100        100  100                                       Johnsongrass 60     100        95   95                                        ______________________________________                                         *Average of two tests  where average is not a multiple of five, given as      next lower multiple of five.                                             

                  TABLE 4                                                         ______________________________________                                        POSTEMERGENCE HERBICIDAL ACTIVITY (% Control)                                 ______________________________________                                        Compound No. 1      2          3    4                                         Rate (kg/ha) 0.3    0.3        0.25 0.3                                       ______________________________________                                        Species                                                                       Soybean      60     85         95   95                                        Wheat        85     100        95   100                                       Corn         70     100        95   100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    90     --         100  100                                       Cocklebur    50     100        100  100                                       Blackgrass   30     90         95   100                                       Green foxtail                                                                              100    100        100  100                                       Johnsongrass 80     100        90   100                                       ______________________________________                                        Compound No. 5      6          7    8                                         Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      80     90         95   40                                        Wheat        95     100        100  20                                        Corn         100    100        100  40                                        Velvetleaf   100    100        100  70                                        Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        100  40                                        Blackgrass   40     100        100  0                                         Green foxtail                                                                              100    100        100  70                                        Johnsongrass 95     100        90   10                                        ______________________________________                                        Compound No. 9      10         11   12                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    95         80   95                                        Wheat        100    100        95   100                                       Corn         100    100        100  100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    95         100  100                                       Cocklebur    100    95         100  --                                        Blackgrass   100    100        95   100                                       Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    95         100  100                                       ______________________________________                                        Compound No. 13     14*        15   16                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      70     50         50   75                                        Wheat        20     50         95   100                                       Corn         75     75         95   95                                        Velvetleaf   80     100        100  100                                       Morningglory 60     100        100  100                                       Chickweed    0      5          10   100                                       Cocklebur    60     55         60   100                                       Blackgrass   5      10         5    60                                        Green foxtail                                                                              20     90         100  100                                       Johnsongrass 40     35         70   95                                        ______________________________________                                        Compound No. 17     18         19   20                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      60     85         60   70                                        Wheat        30     100        100  95                                        Corn         95     100        100  100                                       Velvetleaf   100    100        100  100                                       Morningglory 95     100        100  100                                       Chickweed    20     100        100  80                                        Cocklebur    80     100        100  90                                        Blackgrass   10     95         100  70                                        Green foxtail                                                                              30     100        100  100                                       Johnsongrass 85     100        95   100                                       ______________________________________                                        Compound No. 21     22         23   24                                        Rate (kg/ha) 0.3    0.3        0.3  0.25                                      ______________________________________                                        Species                                                                       Soybean      30     70         40   90                                        Wheat        20     100        15   20                                        Corn         30     90         30   100                                       Velvetleaf   95     100        80   100                                       Morningglory 100    100        100  100                                       Chickweed    20     95         40   100                                       Cocklebur    80     --         20   100                                       Blackgrass   20     95         5    60                                        Green foxtail                                                                              95     100        15   85                                        Johnsongrass 90     70         10   70                                        ______________________________________                                        Compound No. 25     26         27   28                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      75     60         95   95                                        Wheat        10     20         15   90                                        Corn         75     75         100  80                                        Velvetleaf   100    60         100  90                                        Morningglory 100    100        100  95                                        Chickweed    100    20         100  95                                        Cocklebur    100    100        100  70                                        Blackgrass   0      0          10   85                                        Green foxtail                                                                              80     0          90   20                                        Johnsongrass 95     10         50   40                                        ______________________________________                                        Compound No. 29     30         31   32                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      90     90         40   95                                        Wheat        30     20         15   10                                        Corn         80     80         100  80                                        Velvetleaf   100    100        100  100                                       Morningglory 100    95         100  100                                       Chickweed    100    95         30   100                                       Cocklebur    90     100        85   --                                        Blackgrass   0      10         0    0                                         Green foxtail                                                                              50     80         80   60                                        Johnsongrass 0      60         30   20                                        ______________________________________                                        Compound No. 33     34         35   36                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      70     10         60   40                                        Wheat        0      10         15   0                                         Corn         50     25         25   80                                        Velvetleaf   100    50         100  100                                       Morningglory 100    90         100  100                                       Chickweed    80     0          100  95                                        Cocklebur    80     10         80   95                                        Blackgrass   10     0          0    0                                         Green foxtail                                                                              20     0          50   30                                        Johnsongrass 0      0          50   0                                         ______________________________________                                        Compound No. 37     38         39   40                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      30     20         10   0                                         Wheat        15     0          0    0                                         Corn         10     60         10   15                                        Velvetleaf   85     80         10   0                                         Morningglory 50     100        0    0                                         Chickweed    10     80         20   0                                         Cocklebur    60     --         0    0                                         Blackgrass   10     0          0    0                                         Green foxtail                                                                              10     30         20   0                                         Johnsongrass 4      0          0    0                                         ______________________________________                                        Compound No  41     42         43   44                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      30     70         30   80                                        Wheat        0      10         0    40                                        Corn         30     40         0    70                                        Velvetleaf   100    85         70   100                                       Morningglory 100    100        85   100                                       Chickweed    --     70         0    90                                        Cocklebur    --     90         60   100                                       Blackgrass   0      0          0    0                                         Green foxtail                                                                              20     30         10   20                                        Johnsongrass 50     30         30   10                                        ______________________________________                                        Compound No. 45     46         47   48                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      50     60         80   95                                        Wheat        0      90         95   100                                       Corn         40     75         100  100                                       Velvetleaf   60     100        100  100                                       Morningglory 80     100        100  100                                       Chickweed    0      100        100  100                                       Cocklebur    95     100        100  100                                       Blackgrass   0      80         100  100                                       Green foxtail                                                                              30     100        100  100                                       Johnsongrass 70     100        100  100                                       ______________________________________                                        Compound No. 49     50         51   52                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      75     95         100  100                                       Wheat        95     90         95   100                                       Corn         50     90         100  100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        100  100                                       Blackgrass   100    100        100  85                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        95   100                                       ______________________________________                                        Compound No. 53     54         55   56                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    100        90   90                                        Wheat        100    60         70   95                                        Corn         80     70         50   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        95   100                                       Cocklebur    100    100        100  100                                       Blackgrass   100    60         90   95                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        95   100                                       ______________________________________                                        Compound No. 57     58         59   60                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      80     95         90   100                                       Wheat        85     100        95   90                                        Corn         100    100        60   --                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    95         100  100                                       Blackgrass   95     100        90   75                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        100  100                                       ______________________________________                                        Compound No. 61     62         63   64                                        Rate kg/ha)  0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      95     85         85   75                                        Wheat        40     90         80   85                                        Corn         60     80         75   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        100  100                                       Blackgrass   70     95         75   80                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        95   90                                        ______________________________________                                        Compound No. 65     66         67   68                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      95     40         40   95                                        Wheat        90     0          10   20                                        Corn         70     20         20   60                                        Velvetleaf   100    95         100  100                                       Morningglory 100    80         100  100                                       Chickweed    100    100        95   100                                       Cocklebur    100    100        100  100                                       Blackgrass   85     10         10   70                                        Green foxtail                                                                              100    95         80   100                                       Johnsongrass 100    --         70   95                                        ______________________________________                                        Compound No. 69     70         71   72                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      80     80         95   60                                        Wheat        100    100        100  100                                       Corn         100    100        100  100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        100  100                                       Blackgrass   95     80         80   85                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        100  100                                       ______________________________________                                        Compound No. 73     74         75   76                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      60     50         85   85                                        Wheat        100    85         50   50                                        Corn         100    95         80   60                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    90         100  100                                       Cocklebur    100    90         100  60                                        Blackgrass   100    95         80   100                                       Green foxtail                                                                              100    90         100  100                                       Johnsongrass 95     70         95   85                                        ______________________________________                                        Compound No. 77     78         79   80                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      15     60         70   50                                        Wheat        20     50         70   85                                        Corn         50     80         100  100                                       Velvetleaf   95     100        80   100                                       Morningglory 100    100        100  100                                       Chickweed    --     100        0    90                                        Cocklebur    90     100        90   90                                        Blackgrass   10     20         15   40                                        Green foxtail                                                                              10     95         70   100                                       Johnsongrass 20     85         85   90                                        ______________________________________                                        Compound No. 81     82         83   84                                        Rate (kg/ha) 0.25   0.25       0.3  0.25                                      ______________________________________                                        Species                                                                       Soybean      85     70         50   95                                        Wheat        95     70         15   20                                        Corn         100    80         70   50                                        Velvetleaf   100    95         40   30                                        Morningglory 100    100        40   80                                        Chickweed    --     90         10   15                                        Cocklebur    80     85         60   85                                        Blackgrass   95     90         5    0                                         Green foxtail                                                                              100    100        85   60                                        Johnsongrass 85     800        40   50                                        ______________________________________                                        Compound No. 85     86         87   88                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      95     100        95   80                                        Wheat        45     90         40   85                                        Corn         100    85         75   100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        80   100                                       Blackgrass   75     95         90   90                                        Green foxtail                                                                              100    90         95   100                                       Johnsongrass 100    95         95   100                                       ______________________________________                                        Compound No. 89     90         91   92                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      95     100        100  100                                       Wheat        95     95         100  40                                        Corn         100    100        100  75                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        ND   100                                       Blackgrass   100    100        80   90                                        Green foxtail                                                                              100    100        100  100                                       Johnsongrass 100    100        100  100                                       ______________________________________                                        Compound No. 93     94         95   96                                        Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      90     100        100  100                                       Wheat        100    85         90   95                                        Corn         100    75         95   100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        95   100                                       Blackgrass   100    100        100  95                                        Green foxtail                                                                              100    90         100  100                                       Johnsongrass 100    100        100  100                                       ______________________________________                                        Compound No. 97     98         99   100                                       Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      100    85         60   90                                        Wheat        ND     40         40   30                                        Corn         80     70         70   95                                        Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    100        100  100                                       Blackgrass   80     30         30   70                                        Green foxtail                                                                              90     90         70   80                                        Johnsongrass 95     90         70   95                                        ______________________________________                                        Compound No. 101    102        103  104                                       Rate (kg/ha) 0.3    0.3        0.3  0.3                                       ______________________________________                                        Species                                                                       Soybean      80     90         95   100                                       Wheat        10     70         100  90                                        Corn         90     80         95   100                                       Velvetleaf   100    100        100  100                                       Morningglory 100    100        100  100                                       Chickweed    100    100        100  100                                       Cocklebur    100    85         100  100                                       Blackgrass   40     80         60   20                                        Green foxtail                                                                              90     100        100  100                                       Johnsongrass 100    100        100  100                                       ______________________________________                                         *Average of two tests  where average is not a multiple of five, given as      next lower multiple of five.                                             

I claim:
 1. A herbicidal composition comprising a herbicidally effectiveamount of a mixture of a compound of the formula ##STR29## in which A is##STR30## Q is1-methyl-6-trifluoromethyl-2,4-(1H,3H)pyrimidinedione-3-yl; R ishydrogen, M, lower alkyl, cycloalkyl, lower alkenyl, or lower alkynyl,each optionally substituted with one or more chlorine or fluorine, or --CHR⁷ --(CH2)_(m) O!_(n) R⁸ ;R' is hydrogen or methyl; R" is --OR oramino, phenylamino, lower alkyl amino, lower alkenylamino, loweralkoxyamino, cyano, or lower alkyl-, lower haloalkyl-, or phenylsulfonylamino of the formula --N(lower alkyl)-SO₂ R⁹ or --NHSO₂ R⁹ ; R⁷is H or CH₃ ; R⁸ is lower alkyl; R⁹ is lower alkyl, lower haloalkyl, orphenyl; X is hydrogen, methyl, fluorine, or chlorine; Y is hydrogen; Wis oxygen or sulfur; Z is hydrogen, fluorine, chlorine, bromine, loweralkyl, or methoxy; Z' is hydrogen, fluorine, or chlorine; m is 0 to 2,and n is 0 to 6; M is sodium, potassium, or ammonium; and the group AO--may be in the 2, 3, or 4 position of the phenyl ring, and a herbicidehaving a different structure in admixture with a suitable carrier.
 2. Acomposition of claim 1 in which R" is --OR; X is hydrogen, fluorine, orchlorine; and Z is hydrogen, chlorine, or lower alkyl.
 3. A compositionof claim 2 in whichR is lower alkyl, lower chloroalkyl, or -- CHR⁷--(CH2)_(m) O!_(n) R⁸ ; R' is methyl; Z is in the 4-position; Z' ishydrogen or chlorine in the 3-position; m is 0 or 1, n is 1 to 3; andthe group AO-- is in the 2-position of the phenyl ring.
 4. A compositionof claim 3 in which R is methyl, 2,2,2-trichloroethyl, or CH₃O(CH₂)--O--(CH₂)₂ --; X is hydrogen or fluorine; W is oxygen, and Z' ishydrogen, and the herbicide of different structure is agrass-controlling herbicide.
 5. The composition of claim 4 in which Rand Z are each methyl, and X is hydrogen.
 6. The composition of claim 4in which R is methyl, and X is hydrogen, and Z is ethyl.
 7. Thecomposition of claim 4 in which R and Z are each methyl, and X isfluorine.
 8. The composition of claim 4 in which R is methyl, and X isfluorine, and Z is ethyl.
 9. The composition of claim 4 in which R is2,2,2-trichloroethyl, X is hydrogen, and Z is methyl.
 10. Thecomposition of claim 4 in which R is 2,2,2-trichloroethyl, X ishydrogen, and Z is ethyl.
 11. The composition of claim 4 in which R ismethyl, X is hydrogen, and z is ethyl.
 12. A composition of claim 4 inwhich the grass-controlling herbicide is glyphosate, sephoxydim,quizalofop, or fluazifop.
 13. A composition of claim 3 in which Q is1-methyl-6-trifluoromethyl-2,4-(1H,3H)pyrimidinedione-3-yl; R is methyl,2,2,2-trichloroethyl, or CH₃ O(CH₂)--O--(CH₂)₂ --; X is hydrogen orfluorine; W is oxygen, and Z' is hydrogen, and the herbicide ofdifferent structure is a broadleaf herbicide.
 14. A composition of claim13 in which the broadleaf herbicide is 2,4-D or clethodim.